ANKLE2

Chr 12AR

ankyrin repeat and LEM domain containing 2

Also known as: KIAA0692, LEMD7, Lem4, MCPH16

This gene encodes a LEM family inner nuclear membrane protein that promotes dephosphorylation of BAF during mitotic exit to facilitate nuclear envelope reassembly and is involved in brain development. Mutations cause primary microcephaly 16, a neurodevelopmental disorder characterized by reduced brain size present from birth. The condition follows autosomal recessive inheritance.

OMIMResearchSummary from RefSeq, OMIM, UniProt
DNmechanismARLOEUF 0.851 OMIM phenotype
Clinical SummaryANKLE2
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.85LOEUF
pLI 0.000
Z-score 2.29
OE 0.59 (0.420.85)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.34Z-score
OE missense 0.96 (0.891.03)
509 obs / 531.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.59 (0.420.85)
00.351.4
Missense OE0.96 (0.891.03)
00.61.4
Synonymous OE1.10
01.21.6
LoF obs/exp: 22 / 37.1Missense obs/exp: 509 / 531.2Syn Z: -1.18
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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

ANKLE2 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
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