SHH

Chr 7q36.3

sonic hedgehog signaling molecule

Aliases:: HHG1, SMMCI, TPT, TPTPS, MCOPCB5
MANE:: ENST00000297261.7

OMIM: 600725 ↗NCBI: 6469 ↗Ensembl ↗

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Predicted protein structure

AlphaFold predicted structure

SHH · Q15465

v62025-08-01

Predicted Aligned Error matrix for SHH — diagonal shows residue index, colour shows pairwise prediction confidence (lower is better) — Predicted Aligned Error

Mean pLDDT

78.4/ 100

Confident

462 residues

Confidence breakdown

Very high(≥ 90)47%
Confident(70–90)27%
Low(50–70)10%
Very low(< 50)17%

Open interactive 3D viewer

AlphaFold (Jumper et al., 2021) · CC BY 4.0

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

Anophthalmia or microphthalmia
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Clefting
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
DDG2P
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Fetal anomalies
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Holoprosencephaly
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Intellectual disability
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Pituitary hormone deficiency
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

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Disease associations (Open Targets)

holoprosencephaly 3
0.84
holoprosencephaly
0.75
solitary median maxillary central incisor syndrome
0.72
microphthalmia, isolated, with coloboma 5
0.71
Solitary median maxillary central incisor
0.64
Triphalangeal thumb - polysyndactyly syndrome
0.62
schizencephaly
0.62
triphalangeal thumb-polysyndactyly syndrome
0.60
polydactyly of a triphalangeal thumb
0.53
microphthalmia, isolated, with coloboma
0.47

Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.

Protein function (UniProt)

Sonic hedgehog protein

Precursor of sonic hedgehog, a morphogen that activates the smoothened signaling pathway, and which is essential for a variety of patterning events during development (PubMed:29954986, PubMed:29995851, PubMed:30139912, PubMed:31127104, PubMed:31548691). The C-terminal part of the precursor displays an autoproteolysis and a cholesterol transferase activity, resulting (1) in the cleavage of the full-length protein into two parts, Sonic hedgehog protein N-product and C-product (ShhN and ShhC, respectively) and (2) covalent attachment of a cholesterol moiety to the C-terminus of the newly generated ShhN (By similarity). Both autoproteolysis and a cholesterol transferase activities occur in the endoplasmic reticulum (By similarity). Following additional lipidation, ShhN acts as a morphogen, while ShhC is degraded in the endoplasmic reticulum (By similarity)