STARD13

Chr 13

StAR related lipid transfer domain containing 13

Also known as: ARHGAP37, DLC2, GT650, LINC00464

NCBI Gene: 90627 ENSG00000133121 UniProt: Q9Y3M8

This protein functions as a GTPase-activating protein for RhoA and possibly Cdc42, regulating cytoskeletal reorganization, cell proliferation, and cell motility. Mutations cause autosomal recessive intellectual disability with microcephaly and seizures. The gene is moderately constrained against loss-of-function variants (LOEUF 0.641), consistent with recessive inheritance where biallelic mutations are required for disease.

ResearchSummary from RefSeq, UniProt

This gene encodes a protein which contains an N-terminal sterile alpha motif (SAM) for protein-protein interactions, followed by an ATP/GTP-binding motif, a GTPase-activating protein (GAP) domain, and a C-terminal STAR-related lipid transfer (START) domain. It may be involved in regulation of cytoskeletal reorganization, cell proliferation, and cell motility, and acts as a tumor suppressor in hepatoma cells. The gene is located in a region of chromosome 13 that is associated with loss of heterozygosity in hepatocellular carcinomas. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Aug 2011]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.64

LOEUF

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.64LOEUF

pLI 0.000

Z-score 3.53

OE 0.45 (0.32–0.64)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.26Z-score

OE missense 0.97 (0.91–1.04)

624 obs / 642.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.45 (0.32–0.64)

0≤0.351.4

Missense OE?0.97 (0.91–1.04)

0≤0.61.4

Synonymous OE?1.17

0≤1.21.6

LoF obs/exp: 21 / 47.2Missense obs/exp: 624 / 642.2Syn Z: -2.15

Background carrier burden — how many people carry a rare variant somewhere in STARD13?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 28

1,627 rare PASS variants

Rare truncating (LoF)

1 in 1,400

150 rare PASS variants

Rare synonymous (reference)

1 in 52

652 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for STARD13. 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 49	1 in 1,600
South Asian	~43k	1 in 27	1 in 1,300
Remaining (unassigned)	~30k	1 in 20	1 in 1,100
European (Finnish)	~27k	1 in 86	≈ 1 in 6,100
Admixed American	~22k	1 in 26	1 in 2,300
African / African American	~21k	1 in 35	1 in 1,200
East Asian	~20k	1 in 39	1 in 460
Ashkenazi Jewish	~13k	1 in 120	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 32	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 14 coding exons well covered in gnomAD exomes and genomes.? see exons ↓