SH2D3C

Chr 9

SH2 domain containing 3C

Also known as: CHAT, NSP3, PRO34088, SHEP1

NCBI Gene: 10044ENSG00000095370UniProt: Q8N5H7

This gene encodes an adaptor protein and member of a cytoplasmic protein family involved in cell migration. The encoded protein contains a putative Src homology 2 (SH2) domain and guanine nucleotide exchange factor-like domain which allows this signaling protein to form a complex with scaffolding protein Crk-associated substrate. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2011]

148
ClinVar variants
42
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— SH2D3C
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
42 Pathogenic / Likely Pathogenic· 95 VUS of 148 total submissions
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.59LOEUF
pLI 0.000
Z-score 3.41
OE 0.36 (0.23–0.59)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.95Z-score
OE missense 0.76 (0.70–0.83)
415 obs / 542.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.36 (0.23–0.59)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.76 (0.70–0.83)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.96
0≤1.21.6
LoF obs/exp: 12 / 33.2Missense obs/exp: 415 / 542.6Syn Z: 0.51

ClinVar Variant Classifications

148 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic41
Likely Pathogenic1
VUS95
Likely Benign10
Benign1
41
Pathogenic
1
Likely Pathogenic
95
VUS
10
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
41
0
41
Likely Pathogenic
0
0
1
0
1
VUS
0
93
2
0
95
Likely Benign
0
7
0
3
10
Benign
0
0
0
1
1
Total0100444148

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

View in ClinVar →

Protein Context — Lollipop Plot

SH2D3C · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Correction: Yeh et al. Identification of NSP3 (SH2D3C) as a Prognostic Biomarker of Tumor Progression and Immune Evasion for Lung Cancer and Evaluation of Organosulfur Compounds from Allium sativum L. as Therapeutic Candidates. Biomedicines 2021, 9, 1582.
Yeh YC et al.·Biomedicines
2025🔓 Open Access
Long noncoding RNA Sh2d3c promotes manganese-induced neuronal apoptosis through the mmu-miR-675-5p/Chmp4b/Bax axis.
Lu W et al.·Toxicol Lett
2022
Identification of NSP3 (SH2D3C) as a Prognostic Biomarker of Tumor Progression and Immune Evasion for Lung Cancer and Evaluation of Organosulfur Compounds from Allium sativum L. as Therapeutic Candidates.
Yeh YC et al.·Biomedicines
2021🔓 Open Access
The adaptor protein Sh2d3c is critical for marginal zone B cell development and function.
Al-Shami A et al.·J Immunol
2010
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools