FAM193A

Chr 4

family with sequence similarity 193 member A

Also known as: C4orf8, RES4-22

NCBI Gene: 8603 ENSG00000125386 UniProt: P78312 OMIM: 620037

FAM193A encodes a protein that positively regulates p53 by interacting with and destabilizing the p53 repressor MDM4, thereby enhancing p53 transcriptional activity. Mutations cause neurodevelopmental disorders with intellectual disability and developmental delay. The gene follows an autosomal dominant inheritance pattern and is highly constrained against loss-of-function variants.

OMIM ResearchSummary from UniProt

Involved in positive regulation of signal transduction by p53 class mediator. Located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Jun 2026]

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.21

LOEUF· LoF intol.

LOF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.21LOEUF

pLI 1.000

Z-score 5.85

OE 0.10 (0.05–0.21)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

0.91Z-score

OE missense 0.90 (0.85–0.96)

647 obs / 715.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.10 (0.05–0.21)

0≤0.351.4

Missense OE?0.90 (0.85–0.96)

0≤0.61.4

Synonymous OE?1.12

0≤1.21.6

LoF obs/exp: 5 / 49.3Missense obs/exp: 647 / 715.1Syn Z: -1.64

Background carrier burden — how many people carry a rare variant somewhere in FAM193A?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 27

1,938 rare PASS variants

Rare truncating (LoF)

1 in 1,900

74 rare PASS variants

Rare synonymous (reference)

1 in 44

862 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for FAM193A. 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 35	1 in 2,500
South Asian	~43k	1 in 27	1 in 1,200
Remaining (unassigned)	~30k	1 in 29	none seen
European (Finnish)	~27k	1 in 51	1 in 2,700
Admixed American	~22k	1 in 32	1 in 810
African / African American	~21k	1 in 29	1 in 4,000
East Asian	~20k	1 in 31	≈ 1 in 8,800
Ashkenazi Jewish	~13k	1 in 76	≈ 1 in 5,300
Middle Eastern	~2,884	1 in 37	≈ 1 in 1,500

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): 15 of 21 coding exons well covered in gnomAD exomes; exons 1, 2, 3, 4 poorly covered; exons 14, 20 marginal. Genomes: all 21.? see exons ↓