SHARPIN

Chr 8AR

SHANK associated RH domain interactor

Also known as: AIFID, SIPL1

NCBI Gene: 81858ENSG00000179526UniProt: Q9H0F6

Enables polyubiquitin modification-dependent protein binding activity. Involved in defense response to bacterium; protein linear polyubiquitination; and regulation of signal transduction. Located in cytosol. Part of LUBAC complex. [provided by Alliance of Genome Resources, Jul 2025]

Research Assistant →

Primary Disease Associations & Inheritance

Autoinflammation with episodic fever and immune dysregulationMIM #620795
AR
0
Active trials
13
Pubs (1 yr)
64
P/LP submissions
0%
P/LP missense
0.98
LOEUF
GOF
Mechanism· predicted
Clinical Summary— SHARPIN
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
63 unique Pathogenic / Likely Pathogenic· 77 VUS of 174 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.98LOEUF
pLI 0.000
Z-score 1.63
OE 0.58 (0.35–0.98)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-0.04Z-score
OE missense 1.01 (0.90–1.13)
215 obs / 213.2 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.58 (0.35–0.98)
0≤0.351.4
Missense OE1.01 (0.90–1.13)
0≤0.61.4
Synonymous OE1.25
0≤1.21.6
LoF obs/exp: 10 / 17.3Missense obs/exp: 215 / 213.2Syn Z: -1.92
DN
0.5674th %ile
GOF
0.6345th %ile
LOF
0.3259th %ile

The highest-scoring mechanism for this gene is gain-of-function.

GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

174 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic58
Likely Pathogenic5
VUS77
Likely Benign6
Benign6
58
Pathogenic
5
Likely Pathogenic
77
VUS
6
Likely Benign
6
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
0
56
0
58
Likely Pathogenic
0
0
5
0
5
VUS
0
66
11
0
77
Likely Benign
0
5
0
1
6
Benign
0
2
2
2
6
Total273743152

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

SHARPIN · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients