FAM168A

Chr 11

family with sequence similarity 168 member A

Also known as: KIAA0280, TCRP1

NCBI Gene: 23201 ENSG00000054965 UniProt: Q92567

The protein positively regulates base-excision repair and protects cells from DNA damage-induced apoptosis by stabilizing DNA polymerase beta and activating PI3K/AKT/NFKB signaling pathways. Mutations cause autosomal recessive intellectual disability with microcephaly, typically presenting in early childhood. This gene is highly constrained against loss-of-function variants, indicating that complete loss of protein function is likely not tolerated.

ResearchSummary from RefSeq, UniProt

Involved in positive regulation of base-excision repair. [provided by Alliance of Genome Resources, Jul 2025]

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

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P/LP missense

0.23

LOEUF· LoF intol.

LOF

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

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.23LOEUF

pLI 0.987

Z-score 3.35

OE 0.00 (0.00–0.23)

Highly constrained

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

Missense Constraint?

1.66Z-score

OE missense 0.61 (0.51–0.73)

89 obs / 145.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.23)

0≤0.351.4

Missense OE?0.61 (0.51–0.73)

0≤0.61.4

Synonymous OE?0.98

0≤1.21.6

LoF obs/exp: 0 / 13.1Missense obs/exp: 89 / 145.5Syn Z: 0.14

Background carrier burden — how many people carry a rare variant somewhere in FAM168A?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 340

239 rare PASS variants

Rare truncating (LoF)

1 in 23,000

12 rare PASS variants

Rare synonymous (reference)

1 in 200

133 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for FAM168A. 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 380	1 in 21,000
South Asian	~43k	1 in 210	none seen
Remaining (unassigned)	~30k	1 in 290	≈ 1 in 15,000
European (Finnish)	~27k	1 in 810	none seen
Admixed American	~22k	1 in 210	none seen
African / African American	~21k	1 in 260	≈ 1 in 9,200
East Asian	~20k	1 in 420	none seen
Ashkenazi Jewish	~13k	1 in 1,900	none seen
Middle Eastern	~2,884	1 in 240	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 6 coding exons well covered in gnomAD exomes and genomes.? see exons ↓