Seroatlas · Human Serome Atlas

HHIP

Hedgehog-interacting protein

Also known as: FLJ20992, HHIP_HUMAN, HIP

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

Protein identityUniProt · HPA

UniProt accession
Q96QV1
Gene
HHIP
Ensembl
ENSG00000164161
Chromosome
4
Canonical length
700 aa
Protein class
Predicted membrane proteins, Predicted secreted proteins
Subcellular location
Nucleoplasm
Secretome location
Secreted in other tissues

OverviewNCBI Gene

This gene encodes a member of the hedgehog-interacting protein (HHIP) family. The hedgehog (HH) proteins are evolutionarily conserved protein, which are important morphogens for a wide range of developmental processes, including anteroposterior patterns of limbs and regulation of left-right asymmetry in embryonic development. Multiple cell-surface receptors are responsible for transducing and/or regulating HH signals. The HHIP encoded by this gene is a highly conserved, vertebrate-specific inhibitor of HH signaling. It interacts with all three HH family members, SHH, IHH and DHH. Two single nucleotide polymorphisms (SNPs) near this gene are significantly associated with risk of chronic obstructive pulmonary disease (COPD). A single nucleotide polymorphism in this gene is also strongly associated with human height.[provided by RefSeq, Feb 2011]

Canonical amino-acid sequenceUniProt

700 residues, UniProt reviewed canonical sequence.

>Q96QV1|HHIP
     1  MLKMLSFKLL LLAVALGFFE GDAKFGERNE GSGARRRRCL NGNPPKRLKR RDRRMMSQLE
    61  LLSGGEMLCG GFYPRLSCCL RSDSPGLGRL ENKIFSVTNN TECGKLLEEI KCALCSPHSQ
   121  SLFHSPEREV LERDLVLPLL CKDYCKEFFY TCRGHIPGFL QTTADEFCFY YARKDGGLCF
   181  PDFPRKQVRG PASNYLDQME EYDKVEEISR KHKHNCFCIQ EVVSGLRQPV GALHSGDGSQ
   241  RLFILEKEGY VKILTPEGEI FKEPYLDIHK LVQSGIKGGD ERGLLSLAFH PNYKKNGKLY
   301  VSYTTNQERW AIGPHDHILR VVEYTVSRKN PHQVDLRTAR VFLEVAELHR KHLGGQLLFG
   361  PDGFLYIILG DGMITLDDME EMDGLSDFTG SVLRLDVDTD MCNVPYSIPR SNPHFNSTNQ
   421  PPEVFAHGLH DPGRCAVDRH PTDININLTI LCSDSNGKNR SSARILQIIK GKDYESEPSL
   481  LEFKPFSNGP LVGGFVYRGC QSERLYGSYV FGDRNGNFLT LQQSPVTKQW QEKPLCLGTS
   541  GSCRGYFSGH ILGFGEDELG EVYILSSSKS MTQTHNGKLY KIVDPKRPLM PEECRATVQP
   601  AQTLTSECSR LCRNGYCTPT GKCCCSPGWE GDFCRTAKCE PACRHGGVCV RPNKCLCKKG
   661  YLGPQCEQVD RNIRRVTRAG ILDQIIDMTS YLLDLTSYIV

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against HHIP 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)
0.32
Highest tissue expression
15 nTPM

Expression across tissuesHPA

Tissue

  • lung: 15 nTPM
  • hippocampal formation: 8.4 nTPM
  • spinal cord: 6.7 nTPM
  • liver: 6.3 nTPM
  • cerebral cortex: 6.1 nTPM
  • midbrain: 6.1 nTPM

Single-cell type

  • oligodendrocytes: 655 nCPM
  • alveolar cells type 2: 466 nCPM
  • leydig cells: 361 nCPM
  • retinal bipolar cells: 119 nCPM
  • mesothelial cells: 113 nCPM
  • cardiomyocytes: 108 nCPM

Immune cell

  • plasmacytoid DC: 0.4 nTPM
  • basophil: 0 nTPM
  • classical monocyte: 0 nTPM
  • eosinophil: 0 nTPM
  • gdT-cell: 0 nTPM
  • intermediate monocyte: 0 nTPM

Brain region

  • white matter: 93 nTPM
  • basal ganglia: 68 nTPM
  • medulla oblongata: 58 nTPM
  • midbrain: 58 nTPM
  • cerebral cortex: 57 nTPM
  • thalamus: 53 nTPM

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)
0.33
gnomAD pLI
0.95
gnomAD missense Z
1.36
DepMap mean gene effect
0.05
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 HHIP 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 HHIP as an antibody target. Whether an autoantibody or antibody against HHIP could matter depends on whether native HHIP is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

HHIP is annotated at the cell surface, where native HHIP 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 HHIP as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

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