Seroatlas · Human Serome Atlas

SMCHD1

Structural maintenance of chromosomes flexible hinge domain-containing protein 1

Also known as: FSHD2, KIAA0650, SMHD1_HUMAN

Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene

Protein identityUniProt · HPA

UniProt accession
A6NHR9
Gene
SMCHD1
Ensembl
ENSG00000101596
Chromosome
18
Canonical length
2005 aa
Protein class
Disease related genes, Human disease related genes, Predicted intracellular proteins
Subcellular location
Nucleoplasm,Nuclear bodies
Quaternary structure
Homodimer

OverviewNCBI Gene

This gene encodes a protein which contains a hinge region domain found in members of the SMC (structural maintenance of chromosomes) protein family. [provided by RefSeq, Dec 2011]

Canonical amino-acid sequenceUniProt

2005 residues, UniProt reviewed canonical sequence.

>A6NHR9|SMCHD1
     1  MAAADGGGPG GASVGTEEDG GGVGHRTVYL FDRREKESEL GDRPLQVGER SDYAGFRACV
    61  CQTLGISPEE KFVITTTSRK EITCDNFDET VKDGVTLYLL QSVNQLLLTA TKERIDFLPH
   121  YDTLVKSGMY EYYASEGQNP LPFALAELID NSLSATSRNI GVRRIQIKLL FDETQGKPAV
   181  AVIDNGRGMT SKQLNNWAVY RLSKFTRQGD FESDHSGYVR PVPVPRSLNS DISYFGVGGK
   241  QAVFFVGQSA RMISKPADSQ DVHELVLSKE DFEKKEKNKE AIYSGYIRNR KPSDSVHITN
   301  DDERFLHHLI IEEKEKDSFT AVVITGVQPE HIQYLKNYFH LWTRQLAHIY HYYIHGPKGN
   361  EIRTSKEVEP FNNIDIEISM FEKGKVPKIV NLREIQDDMQ TLYVNTAADS FEFKAHVEGD
   421  GVVEGIIRYH PFLYDRETYP DDPCFPSKLK DEDDEDDCFI LEKAARGKRP IFECFWNGRL
   481  IPYTSVEDFD WCTPPKKRGL APIECYNRIS GALFTNDKFQ VSTNKLTFMD LELKLKDKNT
   541  LFTRILNGQE QRMKIDREFA LWLKDCHEKY DKQIKFTLFK GVITRPDLPS KKQGPWATYA
   601  AIEWDGKIYK AGQLVKTIKT LPLFYGSIVR FFLYGDHDGE VYATGGEVQI AMEPQALYDE
   661  VRTVPIAKLD RTVAEKAVKK YVEDEMARLP DRLSVTWPEG DELLPNEVRP AGTPIGALRI
   721  EILNKKGEAM QKLPGTSHGG SKKLLVELKV ILHSSSGNKE IISHISQHGG KWPYWFKKME
   781  NIQKLGNYTL KLQVVLNESN ADTYAGRPLP SKAIKFSVKE GKPEKFSFGL LDLPFRVGVP
   841  FNIPLEFQDE FGHTSQLVTD IQPVLEASGL SLHYEEITKG PNCVIRGVTA KGPVNSCQGK
   901  NYNLKVTLPG LKEDSQILKI RLLPGHPRRL KVKPDSEILV IENGTAFPFQ VEVLDESDNI
   961  TAQPKLIVHC KFSGAPNLPV YVVDCSSSGT SILTGSAIQV QNIKKDQTLK ARIEIPSCKD
  1021  VAPVEKTIKL LPSSHVARLQ IFSVEGQKAI QIKHQDEVNW IAGDIMHNLI FQMYDEGERE
  1081  INITSALAEK IKVNWTPEIN KEHLLQGLLP DVQVPTSVKD MRYCQVSFQD DHVSLESAFT
  1141  VRPLPDEPKH LKCEMKGGKT VQMGQELQGE VVIIITDQYG NQIQAFSPSS LSSLSIAGVG
  1201  LDSSNLKTTF QENTQSISVR GIKFIPGPPG NKDLCFTWRE FSDFIRVQLI SGPPAKLLLI
  1261  DWPELKESIP VINGRDLQNP IIVQLCDQWD NPAPVQHVKI SLTKASNLKL MPSNQQHKTD
  1321  EKGRANLGVF SVFAPRGEHT LQVKAIYNKS IIEGPIIKLM ILPDPEKPVR LNVKYDKDAS
  1381  FLAGGLFTDF MISVISEDDS IIKNINPARI SMKMWKLSTS GNRPPANAET FSCNKIKDND
  1441  KEDGCFYFRD KVIPNKVGTY CIQFGFMMDK TNILNSEQVI VEVLPNQPVK LVPKIKPPTP
  1501  AVSNVRSVAS RTLVRDLHLS ITDDYDNHTG IDLVGTIIAT IKGSNEEDTD TPLFIGKVRT
  1561  LEFPFVNGSA EIMSLVLAES SPGRDSTEYF IVFEPRLPLL SRTLEPYILP FMFYNDVKKQ
  1621  QQMAALTKEK DQLSQSIVMY KSLFEASQQL LNEMKCQVEE ARLKEAQLRN ELKIHNIDIP
  1681  TTQQVPHIEA LLKRKLSEQE ELKKKPRRSC TLPNYTKGSG DVLGKIAHLA QIEDDRAAMV
  1741  ISWHLASDMD CVVTLTTDAA RRIYDETQGR QQVLPLDSIY KKTLPDWKRS LPHFRNGKLY
  1801  FKPIGDPVFA RDLLTFPDNV EHCETVFGML LGDTIILDNL DAANHYRKEV VKITHCPTLL
  1861  TRDGDRIRSN GKFGGLQNKA PPMDKLRGMV FGAPVPKQCL ILGEQIDLLQ QYRSAVCKLD
  1921  SVNKDLNSQL EYLRTPDMRK KKQELDEHEK NLKLIEEKLG MTPIRKCNDS LRHSPKVETT
  1981  DCPVPPKRMR REATRQNRII TKTDV

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against SMCHD1 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability
Intracellular
Secreted
No
Transmembrane segments
0
Mean surface accessibility (rSASA)
0.29
Highest tissue expression
23 nTPM

Expression across tissuesHPA

Tissue

  • bone marrow: 23 nTPM
  • lymph node: 23 nTPM
  • spleen: 20 nTPM
  • thymus: 18 nTPM
  • appendix: 17 nTPM
  • tonsil: 15 nTPM

Single-cell type

  • neutrophils: 6,076 nCPM
  • b-cells: 1,336 nCPM
  • t-cells: 1,112 nCPM
  • neutrophil progenitors: 992 nCPM
  • plasma cells: 796 nCPM
  • nk-cells: 605 nCPM

Immune cell

  • neutrophil: 44 nTPM
  • eosinophil: 4.6 nTPM
  • naive B-cell: 4.1 nTPM
  • naive CD4 T-cell: 3.5 nTPM
  • T-reg: 3.5 nTPM
  • memory B-cell: 3.2 nTPM

Brain region

  • cerebral cortex: 11 nTPM
  • cerebellum: 10 nTPM
  • white matter: 8.3 nTPM
  • spinal cord: 7.8 nTPM
  • thalamus: 7.8 nTPM
  • pons: 7.4 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about SMCHD1.

Disease | AllUniProt

Conditions SMCHD1 is implicated in, by any mechanism.

  • Facioscapulohumeral muscular dystrophy 2, digenic (FSHD2) MIM:158901
  • Bosma arhinia microphthalmia syndrome (BAMS) MIM:603457

Disease | GeneticClinVar

142 pathogenic / likely-pathogenic of 1,793 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

  • Facioscapulohumeral muscular dystrophy 2
  • Arrhinia with choanal atresia and microphthalmia syndrome
  • Scapulohumeral muscular dystrophy
  • SMCHD1-related disorder
  • Inborn genetic diseases

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)
0.15
gnomAD pLI
1
gnomAD missense Z
3.63
DepMap mean gene effect
-0.02
DepMap dependency class
selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 6% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

Molecular functions

Cellular components

Protein domainsUniProt · Pfam · InterPro

KeywordsUniProt

InteractionsUniProt · HPA

Protein binding partners of SMCHD1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads SMCHD1 as an antibody target. Whether an autoantibody or antibody against SMCHD1 could matter depends on whether native SMCHD1 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

SMCHD1 is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.

Annotation status

The present source text does not explicitly label SMCHD1 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

Canonical record: https://seroatlas.com/gene/SMCHD1. Study-independent annotations aggregated from UniProt, Human Protein Atlas, PubMed, IEDB, Pfam, InterPro, Gene Ontology, AlphaFold, gnomAD, DepMap, ClinVar, TCGA. Catalog release seroatlas-reviewed-human-uniprot-20260313.

Seroatlas is the reference for exploring autoantibody and antibody serology at the human-protein level: the autoreactome and human serome, multiplex serology (HuProt, HuScan, VirScan, PhIP-Seq).

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