LYPD6B

Chr 2

LY6/PLAUR domain containing 6B

Also known as: CT116, LYPD7

NCBI Gene: 130576 ENSG00000150556 UniProt: Q8NI32

The protein modulates nicotinic acetylcholine receptor activity in a subtype-specific manner, particularly enhancing sensitivity and altering desensitization of certain receptor combinations. Mutations in LYPD6B cause autosomal recessive intellectual disability with microcephaly and behavioral abnormalities. The gene shows low constraint against loss-of-function variants, consistent with the recessive inheritance pattern observed in affected families.

ResearchSummary from RefSeq, UniProt

Enables acetylcholine receptor regulator activity. Predicted to be located in extracellular region and plasma membrane. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

DNmechanismLOEUF 1.13

Clinical Summary— LYPD6B

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Population Constraint (gnomAD)

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

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ClinVar Variants

22 VUS of 41 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.13LOEUF

pLI 0.000

Z-score 1.27

OE 0.60 (0.34–1.13)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.65Z-score

OE missense 0.83 (0.71–0.98)

99 obs / 118.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.60 (0.34–1.13)

0≤0.351.4

Missense OE?0.83 (0.71–0.98)

0≤0.61.4

Synonymous OE?1.07

0≤1.21.6

LoF obs/exp: 7 / 11.7Missense obs/exp: 99 / 118.8Syn Z: -0.34

This gene — mechanism propensity

0.6453th %ile

GOF

0.4973th %ile

LOF

0.3259th %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

41 submitted variants in ClinVar

ClinVar

Classification Summary

VUS22

Likely Benign5

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	22	0	22
Likely Benign	4	1	5
Benign	0	0	0
Total	26	1	27

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

View in ClinVar →

19 pathogenic / likely-pathogenic (of 24) ClinVar copy-number / structural variants overlap LYPD6B — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →