TMEM258

Chr 11

transmembrane protein 258

Also known as: C11orf10, Kud, Kuduk

NCBI Gene: 746 ENSG00000134825 UniProt: P61165

TMEM258 encodes a subunit of the oligosaccharyl transferase complex that catalyzes the initial transfer of glycans to asparagine residues in nascent proteins during N-linked glycosylation in the endoplasmic reticulum. Mutations cause hypomyelination with developmental delay, which presents in infancy with severe global developmental delays, hypotonia, and progressive white matter abnormalities. This follows an autosomal recessive inheritance pattern.

ResearchSummary from RefSeq, UniProt

Predicted to enable oligosaccharyltransferase complex binding activity. Involved in protein N-linked glycosylation. Acts upstream of or within protein secretion and response to endoplasmic reticulum stress. Located in endoplasmic reticulum and membrane. Part of oligosaccharyltransferase complex A and oligosaccharyltransferase complex B. [provided by Alliance of Genome Resources, Jun 2026]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.81

LOEUF

Multiple*

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.81LOEUF

pLI 0.002

Z-score 0.10

OE 0.95 (0.46–1.81)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.36Z-score

OE missense 0.85 (0.66–1.11)

39 obs / 45.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.95 (0.46–1.81)

0≤0.351.4

Missense OE?0.85 (0.66–1.11)

0≤0.61.4

Synonymous OE?0.96

0≤1.21.6

LoF obs/exp: 4 / 4.2Missense obs/exp: 39 / 45.9Syn Z: 0.14

Background carrier burden — how many people carry a rare variant somewhere in TMEM258?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 560

85 rare PASS variants

Rare truncating (LoF)

1 in 7,600

23 rare PASS variants

Rare synonymous (reference)

1 in 1,300

45 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for TMEM258. 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 510	1 in 9,800
South Asian	~43k	1 in 480	1 in 1,900
Remaining (unassigned)	~30k	1 in 840	≈ 1 in 30,000
European (Finnish)	~27k	1 in 1,900	≈ 1 in 27,000
Admixed American	~22k	1 in 490	≈ 1 in 22,000
African / African American	~21k	1 in 1,300	none seen
East Asian	~20k	1 in 740	1 in 990
Ashkenazi Jewish	~13k	none seen	≈ 1 in 13,000
Middle Eastern	~2,884	≈ 1 in 580	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.