FAM13A

Chr 4

family with sequence similarity 13 member A

Also known as: ARHGAP48, FAM13A1

NCBI Gene: 10144 ENSG00000138640 UniProt: O94988 OMIM: 613299

The FAM13A protein functions as a GTPase activator that regulates small GTPase-mediated signal transduction in the cytosol. This gene is extremely intolerant to loss-of-function mutations and has been implicated in chronic obstructive pulmonary disease, though specific pediatric neurogenetic disorders caused by FAM13A mutations are not established in the provided data. The inheritance pattern for FAM13A-related conditions has not been determined from the available information.

OMIM ResearchSummary from RefSeq

Predicted to enable GTPase activator activity. Predicted to be involved in regulation of small GTPase mediated signal transduction. Predicted to be located in cytosol. Implicated in chronic obstructive pulmonary disease. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 0.83

Clinical Summary— FAM13A

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

2 unique Pathogenic / Likely Pathogenic· 122 VUS of 169 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?

0.83LOEUF

pLI 0.000

Z-score 2.64

OE 0.63 (0.49–0.83)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.80Z-score

OE missense 0.91 (0.84–0.97)

510 obs / 563.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.63 (0.49–0.83)

0≤0.351.4

Missense OE?0.91 (0.84–0.97)

0≤0.61.4

Synonymous OE?0.90

0≤1.21.6

LoF obs/exp: 38 / 60.1Missense obs/exp: 510 / 563.5Syn Z: 1.13

This gene — mechanism propensity

0.7230th %ile

GOF

0.5660th %ile

LOF

0.3452th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction 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

169 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1

Likely Pathogenic1

VUS122

Likely Benign9

Benign7

Conflicting1

Pathogenic

Likely Pathogenic

122

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	1	0	1
Likely Pathogenic	0	0	1	0	1
VUS	0	121	0	1	122
Likely Benign	0	5	1	3	9
Benign	0	1	4	2	7
Conflicting	—				1
Total	0	127	7	6	141

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

View in ClinVar →

28 pathogenic / likely-pathogenic (of 32) ClinVar copy-number / structural variants overlap FAM13A — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →