AFG2B

Chr 15AR

AAA ATPase AFG2B

Also known as: DFNB119, NEDHLS, SPATA5L1

This protein functions as an ATP-dependent chaperone essential for ribosomal large subunit biogenesis and maintains replication fork progression and genome stability as part of a chromatin-associated ATPase complex. Mutations cause autosomal recessive nonsyndromic deafness and a neurodevelopmental disorder with hearing loss and spasticity. The gene shows minimal constraint against loss-of-function variants (pLI near zero), consistent with its autosomal recessive inheritance pattern.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 1.072 OMIM phenotypes
Clinical SummaryAFG2B
🧬
Gene-Disease Validity (ClinGen)
hearing loss, autosomal recessive 119 · ARLimited

Limited evidence — not for standalone diagnostic reporting

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
33 unique Pathogenic / Likely Pathogenic· 131 VUS of 199 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.07LOEUF
pLI 0.000
Z-score 1.28
OE 0.74 (0.521.07)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.86Z-score
OE missense 0.88 (0.800.96)
346 obs / 394.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.74 (0.521.07)
00.351.4
Missense OE0.88 (0.800.96)
00.61.4
Synonymous OE0.95
01.21.6
LoF obs/exp: 20 / 27.2Missense obs/exp: 346 / 394.1Syn Z: 0.48

ClinVar Variant Classifications

199 submitted variants in ClinVar

Classification Summary

Pathogenic17
Likely Pathogenic16
VUS131
Likely Benign14
Benign8
Conflicting3
17
Pathogenic
16
Likely Pathogenic
131
VUS
14
Likely Benign
8
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
6
0
11
0
17
Likely Pathogenic
3
13
0
0
16
VUS
0
118
13
0
131
Likely Benign
0
5
0
9
14
Benign
0
4
1
3
8
Conflicting
3
Total91402512189

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

View in ClinVar →

Protein Context — Lollipop Plot

AFG2B · 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.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Key Publications
Landmark & review papers · by relevance
PubMed
Top 1 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found