SSH3

Chr 11

slingshot protein phosphatase 3

Also known as: SSH3L

NCBI Gene: 54961 ENSG00000172830 UniProt: Q8TE77 OMIM: 606780

SSH3 encodes a protein phosphatase that dephosphorylates and activates cofilin, an actin-depolymerizing factor that regulates actin filament dynamics. Mutations in SSH3 cause autosomal recessive intellectual disability with microcephaly and variable features including seizures and developmental delay. The gene shows very low constraint against loss-of-function variants, which is consistent with recessive inheritance requiring biallelic mutations for disease manifestation.

OMIM ResearchSummary from RefSeq, UniProt

The ADF (actin-depolymerizing factor)/cofilin family (see MIM 601442) is composed of stimulus-responsive mediators of actin dynamics. ADF/cofilin proteins are inactivated by kinases such as LIM domain kinase-1 (LIMK1; MIM 601329). The SSH family appears to play a role in actin dynamics by reactivating ADF/cofilin proteins in vivo (Niwa et al., 2002 [PubMed 11832213]).[supplied by OMIM, Mar 2008]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

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P/LP missense

—

LOEUF

Multiple*

Mechanism· predicted

Some data sources returned errors (1)

gnomad: Error: gnomAD API error: 400

Population Genetics & Constraint

gnomAD

Constraint data not available from gnomAD.

Background carrier burden — how many people carry a rare variant somewhere in SSH3?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 55

887 rare PASS variants

Rare truncating (LoF)

1 in 730

156 rare PASS variants

Rare synonymous (reference)

1 in 150

334 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for SSH3. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 61	1 in 780
South Asian	~43k	1 in 66	1 in 520
Remaining (unassigned)	~30k	1 in 51	1 in 730
European (Finnish)	~27k	1 in 180	1 in 1,400
Admixed American	~22k	1 in 72	1 in 410
African / African American	~21k	1 in 51	1 in 470
East Asian	~20k	1 in 76	1 in 530
Ashkenazi Jewish	~13k	1 in 330	1 in 2,200
Middle Eastern	~2,884	1 in 65	1 in 580

Each group is summed over the variants that are rare in that group. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.