PLCB3

Chr 11

phospholipase C beta 3

Also known as: SMDCD

NCBI Gene: 5331 ENSG00000149782 UniProt: Q01970

The protein catalyzes the production of second messenger molecules diacylglycerol and inositol 1,4,5-trisphosphate, serving as a key transducer of G protein-coupled receptor signaling. Mutations cause spondylometaphyseal dysplasia with corneal dystrophy, a skeletal dysplasia affecting the spine and metaphyses with associated corneal abnormalities. This gene is highly constrained against loss-of-function variants and follows autosomal recessive inheritance.

ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a member of the phosphoinositide phospholipase C beta enzyme family that catalyze the production of the secondary messengers diacylglycerol and inositol 1,4,5-triphosphate from phosphatidylinositol in G-protein-linked receptor-mediated signal transduction. Alternative splicing results in multiple transcript variants.[provided by RefSeq, May 2010]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtSpondylometaphyseal dysplasia with corneal dystrophy

Clinical highlights

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.31

LOEUF· LoF intol.

LOF

Mechanism· G2P

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

0.31LOEUF

pLI 0.940

Z-score 6.06

OE 0.20 (0.13–0.31)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

3.27Z-score

OE missense 0.67 (0.62–0.72)

512 obs / 766.4 exp

Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?

LoF OE?0.20 (0.13–0.31)

0≤0.351.4

Missense OE?0.67 (0.62–0.72)

0≤0.61.4

Synonymous OE?1.02

0≤1.21.6

LoF obs/exp: 13 / 66.2Missense obs/exp: 512 / 766.4Syn Z: -0.29

Background carrier burden — how many people carry a rare variant somewhere in PLCB3?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 51

1,333 rare PASS variants

Rare truncating (LoF)

1 in 1,600

133 rare PASS variants

Rare synonymous (reference)

1 in 66

758 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for PLCB3. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 66	1 in 1,800
South Asian	~43k	1 in 36	1 in 2,200
Remaining (unassigned)	~30k	1 in 40	1 in 1,200
European (Finnish)	~27k	1 in 120	1 in 1,200
Admixed American	~22k	1 in 37	1 in 2,400
African / African American	~21k	1 in 36	1 in 1,400
East Asian	~20k	1 in 57	1 in 970
Ashkenazi Jewish	~13k	1 in 140	1 in 830
Middle Eastern	~2,884	1 in 39	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 29 of 31 coding exons well covered in gnomAD exomes; exons 1, 23 marginal. Genomes: 30 of 31 (exon 23 below).? see exons ↓