ANKLE2

Chr 12AR

ankyrin repeat and LEM domain containing 2

Also known as: KIAA0692, LEMD7, Lem4, MCPH16

NCBI Gene: 23141ENSG00000176915UniProt: Q86XL3

This gene encodes a member of the LEM family of inner nuclear membrane proteins. The encoded protein functions as a mitotic regulator through postmitotic formation of the nuclear envelope. Mutations in this gene cause morphology defects in the nuclear envelope and BAF hyperphosphorylation. [provided by RefSeq, Mar 2014]

Primary Disease Associations & Inheritance

Microcephaly 16, primary, autosomal recessiveMIM #616681
AR
1
Active trials
34
Pathogenic / LP
390
ClinVar variants
6
Pubs (1 yr)
0.3
Missense Z
0.85
LOEUF
Clinical Summary— ANKLE2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
34 Pathogenic / Likely Pathogenic· 186 VUS of 390 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.85LOEUF
pLI 0.000
Z-score 2.29
OE 0.59 (0.42–0.85)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.34Z-score
OE missense 0.96 (0.89–1.03)
509 obs / 531.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.59 (0.42–0.85)
0≤0.351.4
Missense OE0.96 (0.89–1.03)
0≤0.61.4
Synonymous OE1.10
0≤1.21.6
LoF obs/exp: 22 / 37.1Missense obs/exp: 509 / 531.2Syn Z: -1.18
DN
DN
0.6551th %ile
GOF
0.5366th %ile
LOF
0.3454th %ile

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

390 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic25
Likely Pathogenic9
VUS186
Likely Benign90
Benign71
Conflicting9
25
Pathogenic
9
Likely Pathogenic
186
VUS
90
Likely Benign
71
Benign
9
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
0
24
0
25
Likely Pathogenic
1
3
5
0
9
VUS
2
164
20
0
186
Likely Benign
0
34
26
30
90
Benign
0
5
60
6
71
Conflicting
—9
Total420613536390

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

View in ClinVar →

ANKLE2 · protein map & ClinVar variants

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

Clinical Literature
Landmark / reviewRecent case evidence
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 4 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients