TEX15

protein-coding

testis expressed 15, meiosis and synapsis associated

Gene summary

This gene encodes a protein that is required for DNA double-strand break repair, chromosome synapsis, and meiotic recombination in spermatocytes. Male mice with a knockout of the orthologous gene are viable but sterile. Loss-of-function mutations in the orthologous mouse gene cause early meiotic arrest in spermatocytes, before the mid-pachytene stage. Naturally occurring mutations in this gene are associated with nonobstructive azoospermia. [provided by RefSeq, Apr 2017]

MANE transcript

NM_001350162.2

Inheritance

AD, AR

ClinVar variants

P:30U:285B:101

Top phenotype

Spermatogenic failure 25

gnomAD constraint

pLI —, LoF o/e 0.62

Max pathogenic AF

—

Genomic locus

chr8:30,831,544-30,913,008

External References & Databases

Ensembl (ENSG00000133863)

Transcript & Mutation Effects

hg38 • Region Span ~81.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

spermatogenic failure 25LIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0054729

Submitter: Labcorp Genetics (formerly Invitae)

male infertility with azoospermia or oligozoospermia due to single gene mutationSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0018393

Submitter: Orphanet

Clinical Genomic Database (CGD)

Spermatogenic failure 25AR

Manifestation: Endocrine; Genitourinary

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 26199321; 28303806; 28355598

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TEX15 variants in ClinVar

9 Conditions Cataloged

not specifiedTotal: 306

not providedTotal: 64

Spermatogenic failure 25Total: 47

TEX15-related disorderTotal: 31

Non-obstructive azoospermiaTotal: 5

Male infertility with azoospermia or oligozoospermia due to single gene mutationTotal: 2

EBV-positive nodal T- and NK-cell lymphomaTotal: 1

Myoepithelial tumorTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001350162.2. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				18 clinvar	10 clinvar	28
missense		2 clinvar	281 clinvar	61 clinvar	12 clinvar	356
nonsense	3 clinvar	7 clinvar	2 clinvar			12
start loss						0
frameshift	4 clinvar	14 clinvar	2 clinvar			20
splice donor/acceptor (+/-2bp)						0
Total	7	23	285	79	22	416

Highest pathogenic variant AF is 0.0013814314

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 8 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001350162.2	RefSeq	NP_001337091.1	9	MANE Select
ENST00000643185.2	Ensembl	ENSP00000493555.1	9	MANE Select
ENST00000256246.5	Ensembl	ENSP00000256246.2	4	Standard
ENST00000638951.1	Ensembl	ENSP00000492713.1	10	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

DNA repair
synapsis
male meiotic nuclear division
spermatogenesis
regulation of double-strand break repair via homologous recombination

Cellular Component

nucleus
cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000256246
Coding exons: 4
Length: 59063
Individuals with no LoFs: 123769
Homozygous LoFs: 0
Heterozygous LoFs: 3
Defined: 123772
p: 0.0000121

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-1.15	1483	1.36e+3	1.09	0.0000648	18595
Missense (PolyPhen)		243	269.22	0.90262		4023
Synonymous	-1.47	551	509	1.08	0.0000265	5069
Loss of Function	3.27	53	85.6	0.619	0.00000416	1318

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.0000097	0.0000089	rare
South Asian	0.000078	0.000068	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Required during spermatogenesis for normal chromosome synapsis and meiotic recombination in germ cells. Necessary for formation of DMC1 and RAD51 foci on meiotic chromosomes, suggesting a specific role in DNA double-stranded break repair. {ECO:0000250|UniProtKB:F8VPN2}.;

Recessive Scores

pRec: 0.0693

Intolerance Scores

LoFtool: 0.968
RVIS EVS: 2.71
RVIS percentile EVS: 98.91

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.125

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	Medium	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High