TLCD3B

Chr 16AR

TLC domain containing 3B

Also known as: CORD22, FAM57B, FP1188

NCBI Gene: 83723 ENSG00000149926 UniProt: Q71RH2 OMIM: 615175

The protein is involved in ceramide synthesis and functions as a transmembrane protein that may be targeted by PPAR-gamma. Mutations cause cone-rod dystrophy 22, a retinal degeneration affecting both cone and rod photoreceptors with autosomal recessive inheritance. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.516), suggesting intolerance to complete protein loss.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a transmembrane protein, which may be a likely target of peroxisome proliferator-activated receptor gamma (PPAR-gamma). The product of the orthologous gene in mouse is related to obesity. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Cone-rod dystrophy 22MIM #619531

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Cone-rod dystrophy 22; no ClinGen or GenCC tier

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.52

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.52LOEUF

pLI 0.665

Z-score 2.71

OE 0.16 (0.07–0.52)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.18Z-score

OE missense 0.74 (0.63–0.86)

117 obs / 158.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.16 (0.07–0.52)

0≤0.351.4

Missense OE?0.74 (0.63–0.86)

0≤0.61.4

Synonymous OE?1.00

0≤1.21.6

LoF obs/exp: 2 / 12.2Missense obs/exp: 117 / 158.9Syn Z: -0.01

Background carrier burden — how many people carry a rare variant somewhere in TLCD3B?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 210

424 rare PASS variants

Rare truncating (LoF)

1 in 1,200

61 rare PASS variants

Rare synonymous (reference)

1 in 200

213 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for TLCD3B. 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 240	1 in 1,200
South Asian	~43k	1 in 97	1 in 830
Remaining (unassigned)	~30k	1 in 220	1 in 1,400
European (Finnish)	~27k	1 in 1,200	1 in 1,600
Admixed American	~22k	1 in 130	1 in 1,200
African / African American	~21k	1 in 170	1 in 1,200
East Asian	~20k	1 in 140	1 in 810
Ashkenazi Jewish	~13k	1 in 590	≈ 1 in 3,100
Middle Eastern	~2,884	1 in 160	≈ 1 in 830

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): All 5 coding exons well covered in gnomAD exomes and genomes.? see exons ↓