GLDN

Chr 15AR

gliomedin

Also known as: CLOM, COLM, CRG-L2, CRGL2, LCCS11, UNC-112, UNC-122

NCBI Gene: 342035 ENSG00000186417 UniProt: Q6ZMI3 OMIM: 608603

This gene encodes a protein that contains olfactomedin-like and collagen-like domains. The encoded protein, which exists in both transmembrane and secreted forms, promotes formation of the nodes of Ranvier in the peripheral nervous system. Mutations in this gene cause a form of lethal congenital contracture syndrome in human patients. Autoantibodies to the encoded protein have been identified in sera form patients with multifocal motor neuropathy. [provided by RefSeq, May 2017]

OMIM Research

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Lethal congenital contracture syndrome 11MIM #617194

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · lethal congenital contracture syndrome 11 · AR · ClinGen 2025

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.27

LOEUF

LOF

Mechanism· G2P

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.27LOEUF

pLI 0.000

Z-score 0.52

OE 0.88 (0.63–1.27)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.13Z-score

OE missense 1.02 (0.93–1.12)

303 obs / 296.7 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.88 (0.63–1.27)

0≤0.351.4

Missense OE?1.02 (0.93–1.12)

0≤0.61.4

Synonymous OE?1.13

0≤1.21.6

LoF obs/exp: 21 / 23.8Missense obs/exp: 303 / 296.7Syn Z: -1.07

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

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 86

846 rare PASS variants

Rare truncating (LoF)

1 in 1,000

113 rare PASS variants

Rare synonymous (reference)

1 in 160

355 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for GLDN. 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 110	1 in 1,200
South Asian	~43k	1 in 61	1 in 790
Remaining (unassigned)	~30k	1 in 67	1 in 980
European (Finnish)	~27k	1 in 150	1 in 1,800
Admixed American	~22k	1 in 57	1 in 1,300
African / African American	~21k	1 in 44	1 in 1,500
East Asian	~20k	1 in 130	1 in 1,200
Ashkenazi Jewish	~13k	1 in 270	≈ 1 in 5,600
Middle Eastern	~2,884	1 in 95	≈ 1 in 950

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 10 coding exons well covered in gnomAD exomes and genomes.? see exons ↓