AFG2A

Chr 4AR

AAA ATPase AFG2A

Also known as: AFG2, EHLMRS, NEDHSB, SPAF, SPATA5

AFG2A encodes an ATP-dependent chaperone that is part of a chromatin-associated complex essential for DNA replication fork progression, genome stability, and ribosomal particle maturation. Biallelic mutations cause a neurodevelopmental disorder with hearing loss, seizures, and brain abnormalities with autosomal recessive inheritance. The gene shows very low constraint against loss-of-function variants, consistent with the recessive inheritance pattern observed clinically.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 1.081 OMIM phenotype
Clinical SummaryAFG2A
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Gene-Disease Validity (ClinGen)
syndromic complex neurodevelopmental disorder · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.08LOEUF
pLI 0.000
Z-score 1.14
OE 0.81 (0.621.08)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.46Z-score
OE missense 0.94 (0.871.02)
446 obs / 474.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.81 (0.621.08)
00.351.4
Missense OE0.94 (0.871.02)
00.61.4
Synonymous OE0.94
01.21.6
LoF obs/exp: 34 / 42.0Missense obs/exp: 446 / 474.2Syn Z: 0.60

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

AFG2A · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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