SH2D4A
protein-codingSH2 domain containing 4A, the group of Protein phosphatase 1 regulatory subunits|SH2 domain containing
Gene summary
Enables phosphatase binding activity. Located in cytosol. [provided by Alliance of Genome Resources, Jul 2025]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~82.5 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to SH2D4A variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_022071.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 3 | 3 | ||||
| missense | 83 | 1 | 84 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 88 | 1 | 0 | 89 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_071354.2 | 9 | MANE Select | |
| Ensembl | ENSP00000265807.3 | 9 | MANE Select | |
| RefSeq | NP_001167630.1 | 9 | Standard | |
| RefSeq | NP_001167631.1 | 9 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- negative regulation of phosphatase activity
Molecular Function
- protein binding
- phosphatase binding
Cellular Component
- cytoplasm
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000265807
- Coding exons
- 9
- Length
- 82602
- Individuals with no LoFs
- 125302
- Homozygous LoFs
- 2
- Heterozygous LoFs
- 444
- Defined
- 125748
- p
- 0.00178
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -2.17 | 334 | 240 | 1.39 | 0.0000130 | 2958 |
| Missense (PolyPhen) | 103 | 70.297 | 1.4652 | 843 | ||
| Synonymous | -2.59 | 125 | 93.2 | 1.34 | 0.00000546 | 826 |
| Loss of Function | -0.276 | 32 | 30.4 | 1.05 | 0.00000198 | 310 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00069 | 0.00068 | rare |
| Latino/Admixed American | 0.00092 | 0.00090 | rare |
| Ashkenazi Jewish | 0.0012 | 0.0012 | notable |
| East Asian | 0.0054 | 0.0053 | notable |
| Finnish | 0.00042 | 0.00042 | rare |
| European (Non-Finnish) | 0.0022 | 0.0021 | notable |
| South Asian | 0.0012 | 0.0011 | notable |
| Other | 0.0020 | 0.0018 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Inhibits estrogen-induced cell proliferation by competing with PLCG for binding to ESR1, blocking the effect of estrogen on PLCG and repressing estrogen-induced proliferation. May play a role in T-cell development and function. {ECO:0000269|PubMed:18641339, ECO:0000269|PubMed:19712589}.;
Recessive Scores
- pRec
- 0.0945
Intolerance Scores
- LoFtool
- 0.629
- RVIS EVS
- 0.69
- RVIS percentile EVS
- 85.24
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.788
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | High |
| Cancer | Medium | Medium | Medium |