AFG2A

Chr 4AR

AAA ATPase AFG2A

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

NCBI Gene: 166378ENSG00000145375UniProt: Q8NB90

This gene encodes a member of the ATPase associated with diverse activities family, whose members are defined by a highly conserved ATPase domain. Members of this family participate in diverse cellular processes that include membrane fusion, DNA replication, microtubule severing, and protein degradation. The protein encoded by this gene has a putative mitochondrial targeting sequence and has been proposed to function in maintenance of mitochondrial function and integrity during mouse spermatogenesis. Allelic variants in this gene have been associated with epilepsy, hearing loss, and cognitive disability syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2016]

Primary Disease Associations & Inheritance

Neurodevelopmental disorder with hearing loss, seizures, and brain abnormalitiesMIM #616577
AR
551
ClinVar variants
76
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— AFG2A
🧬
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.
📋
ClinVar Variants
76 Pathogenic / Likely Pathogenic· 157 VUS of 551 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.08LOEUF
pLI 0.000
Z-score 1.14
OE 0.81 (0.62–1.08)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.46Z-score
OE missense 0.94 (0.87–1.02)
446 obs / 474.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.81 (0.62–1.08)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.94 (0.87–1.02)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.94
0≤1.21.6
LoF obs/exp: 34 / 42.0Missense obs/exp: 446 / 474.2Syn Z: 0.60

ClinVar Variant Classifications

551 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic49
Likely Pathogenic27
VUS157
Likely Benign255
Benign48
Conflicting15
49
Pathogenic
27
Likely Pathogenic
157
VUS
255
Likely Benign
48
Benign
15
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
15
3
31
0
49
Likely Pathogenic
6
12
9
0
27
VUS
2
130
23
2
157
Likely Benign
1
4
117
133
255
Benign
0
5
39
4
48
Conflicting
—15
Total24154219139551

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

View 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.

Gene2Phenotype Curations

AFG2A-related epilepsy, hearing loss, and intellectual developmental disorder syndrome

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Neurodevelopmental disorder with hearing loss, seizures, and brain abnormalities

MIM #616577

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found

Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools