FAM53A

Chr 4

family with sequence similarity 53 member A

Also known as: DNTNP

FAM53A is predicted to be involved in protein import into the nucleus and may play an important role in neural development, particularly in the dorsomedial roof of the third ventricle. The gene shows low constraint to loss-of-function variation (pLI 0.004, LOEUF 1.17), and no established human disease associations have been reported to date. Clinical significance of variants in this gene remains uncertain.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
1
Pubs (1 yr)
144
P/LP submissions
0%
P/LP missense
1.17
LOEUF
DN
Mechanism· predicted
Clinical SummaryFAM53A
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
144 unique Pathogenic / Likely Pathogenic· 103 VUS of 278 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.17LOEUF
pLI 0.004
Z-score 1.22
OE 0.56 (0.291.17)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.44Z-score
OE missense 1.08 (0.971.21)
244 obs / 225.2 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.56 (0.291.17)
00.351.4
Missense OE1.08 (0.971.21)
00.61.4
Synonymous OE1.07
01.21.6
LoF obs/exp: 5 / 9.0Missense obs/exp: 244 / 225.2Syn Z: -0.58
DN
0.6648th %ile
GOF
0.5169th %ile
LOF
0.51top 25%

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

278 submitted variants in ClinVar

Classification Summary

Pathogenic137
Likely Pathogenic7
VUS103
Likely Benign14
Benign10
137
Pathogenic
7
Likely Pathogenic
103
VUS
14
Likely Benign
10
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
137
0
137
Likely Pathogenic
0
0
7
0
7
VUS
0
88
15
0
103
Likely Benign
0
10
2
2
14
Benign
0
6
0
4
10
Total01041616271

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

View in ClinVar →

Protein Context — Lollipop Plot

FAM53A · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
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Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC