TESMIN

Chr 11

testis expressed metallothionein like protein

Also known as: CXCDC2, MTL5, MTLT

NCBI Gene: 9633 ENSG00000132749 UniProt: Q9Y4I5 OMIM: 604374

TESMIN encodes a metallothionein-like protein that is essential for normal spermatogenesis and male fertility, specifically required for completion of meiosis in male germ cells. Mutations cause male infertility with meiotic arrest, following an autosomal recessive inheritance pattern. The gene shows extremely high constraint against loss-of-function variants (pLI near 1.0), indicating that biallelic mutations are likely required for disease manifestation.

OMIM ResearchSummary from RefSeq, UniProt

Metallothionein proteins are highly conserved low-molecular-weight cysteine-rich proteins that are induced by and bind to heavy metal ions and have no enzymatic activity. They may play a central role in the regulation of cell growth and differentiation and are involved in spermatogenesis. This gene encodes a metallothionein-like protein which has been shown to be expressed differentially in mouse testis and ovary. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.85

LOEUF

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.85LOEUF

pLI 0.000

Z-score 2.09

OE 0.51 (0.32–0.85)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.16Z-score

OE missense 0.80 (0.71–0.90)

212 obs / 265.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.51 (0.32–0.85)

0≤0.351.4

Missense OE?0.80 (0.71–0.90)

0≤0.61.4

Synonymous OE?0.89

0≤1.21.6

LoF obs/exp: 11 / 21.5Missense obs/exp: 212 / 265.3Syn Z: 0.89

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

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 110

677 rare PASS variants

Rare truncating (LoF)

1 in 1,500

113 rare PASS variants

Rare synonymous (reference)

1 in 230

305 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for TESMIN. 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 140	1 in 1,700
South Asian	~43k	1 in 84	1 in 1,700
Remaining (unassigned)	~30k	1 in 120	1 in 3,200
European (Finnish)	~27k	1 in 290	1 in 3,900
Admixed American	~22k	1 in 130	1 in 790
African / African American	~21k	1 in 68	1 in 690
East Asian	~20k	1 in 80	1 in 1,200
Ashkenazi Jewish	~13k	1 in 420	≈ 1 in 3,400
Middle Eastern	~2,884	1 in 99	1 in 550

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): 8 of 9 coding exons well covered in gnomAD exomes; exon 5 marginal. Genomes: all 9.? see exons ↓