Seroatlas · Human Serome Atlas

SHH

Sonic hedgehog protein

Also known as: HHG1, HLP3, HPE3, MCOPCB5, SHH_HUMAN, SMMCI, TPT, TPTPS

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

Protein identityUniProt · HPA

UniProt accession
Q15465
Gene
SHH
Ensembl
ENSG00000164690
Chromosome
7
Canonical length
462 aa
Protein class
Disease related genes, Human disease related genes, Predicted intracellular proteins
Secretome location
Intracellular and membrane

OverviewNCBI Gene

This gene encodes a protein that is instrumental in patterning the early embryo. It has been implicated as the key inductive signal in patterning of the ventral neural tube, the anterior-posterior limb axis, and the ventral somites. Of three human proteins showing sequence and functional similarity to the sonic hedgehog protein of Drosophila, this protein is the most similar. The protein is made as a precursor that is autocatalytically cleaved; the N-terminal portion is soluble and contains the signalling activity while the C-terminal portion is involved in precursor processing. More importantly, the C-terminal product covalently attaches a cholesterol moiety to the N-terminal product, restricting the N-terminal product to the cell surface and preventing it from freely diffusing throughout the developing embryo. Defects in this protein or in its signalling pathway are a cause of holoprosencephaly (HPE), a disorder in which the developing forebrain fails to correctly separate into right and left hemispheres. HPE is manifested by facial deformities. It is also thought that mutations in this gene or in its signalling pathway may be responsible for VACTERL syndrome, which is characterized by vertebral defects, anal atresia, tracheoesophageal fistula with esophageal atresia, radial and renal dysplasia, cardiac anomalies, and limb abnormalities. Additionally, mutations in a long range enhancer located approximately 1 megabase upstream of this gene disrupt limb patterning and can result in preaxial polydactyly. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

462 residues, UniProt reviewed canonical sequence.

>Q15465|SHH
     1  MLLLARCLLL VLVSSLLVCS GLACGPGRGF GKRRHPKKLT PLAYKQFIPN VAEKTLGASG
    61  RYEGKISRNS ERFKELTPNY NPDIIFKDEE NTGADRLMTQ RCKDKLNALA ISVMNQWPGV
   121  KLRVTEGWDE DGHHSEESLH YEGRAVDITT SDRDRSKYGM LARLAVEAGF DWVYYESKAH
   181  IHCSVKAENS VAAKSGGCFP GSATVHLEQG GTKLVKDLSP GDRVLAADDQ GRLLYSDFLT
   241  FLDRDDGAKK VFYVIETREP RERLLLTAAH LLFVAPHNDS ATGEPEASSG SGPPSGGALG
   301  PRALFASRVR PGQRVYVVAE RDGDRRLLPA AVHSVTLSEE AAGAYAPLTA QGTILINRVL
   361  ASCYAVIEEH SWAHRAFAPF RLAHALLAAL APARTDRGGD SGGGDRGGGG GRVALTAPGA
   421  ADAPGAGATA GIHWYSQLLY QIGTWLLDSE ALHPLGMAVK SS

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against SHH 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
Cell surface
Secreted
No
Transmembrane segments
0
Mean surface accessibility (rSASA)
0.34
Highest tissue expression
15 nTPM

Expression across tissuesHPA

Tissue

  • urinary bladder: 15 nTPM
  • liver: 13 nTPM
  • stomach: 9.9 nTPM
  • adrenal gland: 8.2 nTPM
  • cervix: 4.2 nTPM
  • gallbladder: 3.6 nTPM

Single-cell type

  • urothelial cells: 59 nCPM
  • prostatic hillock cells: 47 nCPM
  • foveolar cells: 42 nCPM
  • papillary tip epithelial cells: 26 nCPM
  • hepatocytes: 25 nCPM
  • epididymal efferent duct absorptive cells: 21 nCPM

Immune cell

  • neutrophil: 0.3 nTPM
  • basophil: 0.2 nTPM
  • plasmacytoid DC: 0.1 nTPM
  • classical monocyte: 0 nTPM
  • eosinophil: 0 nTPM
  • gdT-cell: 0 nTPM

Brain region

  • hypothalamus: 14 nTPM
  • pons: 10 nTPM
  • medulla oblongata: 7.5 nTPM
  • thalamus: 6.1 nTPM
  • cerebellum: 3.9 nTPM
  • midbrain: 3.9 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about SHH.

Disease | AllUniProt

Conditions SHH is implicated in, by any mechanism.

Disease | GeneticClinVar

126 pathogenic / likely-pathogenic of 661 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

  • Holoprosencephaly 3
  • Solitary median maxillary central incisor syndrome
  • SHH-related disorder
  • Schizencephaly
  • See cases

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)
0.24
gnomAD pLI
0.98
gnomAD missense Z
2.95
DepMap mean gene effect
0.15
DepMap dependency class
none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% 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 SHH 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 SHH as an antibody target. Whether an autoantibody or antibody against SHH could matter depends on whether native SHH is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

SHH is annotated at the cell surface, where native SHH is exposed to circulating antibodies and is a prime autoantibody target that could block, deplete, or overstimulate it.

Annotation status

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

Canonical record: https://seroatlas.com/gene/SHH. 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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