ZMYND15

protein-coding

zinc finger MYND-type containing 15, the group of Zinc fingers MYND-type

Gene summary

This gene encodes a MYND-containing zinc-binding protein with a nuclear localization sequence. A similar gene in mice has been shown to act as a testis-specific transcriptional repressor by recruiting histone deacetylase enzymes to regulate spatiotemporal expression of many haploid genes. This protein may play an important role in spermatogenesis. Alternative splicing results in multiple transcript variants and protein isoforms. [provided by RefSeq, Jun 2012]

MANE transcript

NM_001136046.3

Inheritance

AD, AR

ClinVar variants

P:11U:119B:20

Top phenotype

Spermatogenic failure 14

gnomAD constraint

pLI —, LoF o/e 0.63

Max pathogenic AF

—

Genomic locus

chr17:4,739,833-4,746,119

External References & Databases

Ensembl (ENSG00000141497)

Transcript & Mutation Effects

hg38 • Region Span ~6.3 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

male infertility with azoospermia or oligozoospermia due to single gene mutationSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0018393

Submitter: Orphanet

spermatogenic failure 14MODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0014366

Submitter: Ambry Genetics

spermatogenic failure 14STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014366

Submitter: Labcorp Genetics (formerly Invitae)

spermatogenic failure 14STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014366

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Spermatogenic failure 14AR

Manifestation: 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: 24431330

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ZMYND15 variants in ClinVar

6 Conditions Cataloged

not specifiedTotal: 120

Spermatogenic failure 14Total: 11

not providedTotal: 9

ZMYND15-related disorderTotal: 6

Non-obstructive azoospermiaTotal: 1

Male infertilityTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001136046.3. 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			1 clinvar	7 clinvar	1 clinvar	9
missense			114 clinvar	11 clinvar	1 clinvar	126
nonsense	2 clinvar	2 clinvar				4
start loss						0
frameshift	3 clinvar	3 clinvar				6
splice donor/acceptor (+/-2bp)		1 clinvar	4 clinvar			5
Total	5	6	119	18	2	150

Highest pathogenic variant AF is 0.00013720691

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 24 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001136046.3	RefSeq	NP_001129518.1	13	MANE Select
ENST00000433935.6	Ensembl	ENSP00000391742.1	13	MANE Select
NM_001267822.1	RefSeq	NP_001254751.1	13	Standard
NM_032265.2	RefSeq	NP_115641.1	12	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

spermatid development
negative regulation of transcription, DNA-templated

Molecular Function

histone deacetylase binding
metal ion binding

Cellular Component

nucleus
cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000573751
Coding exons: 13
Length: 6093
Individuals with no LoFs: 124075
Homozygous LoFs: 37
Heterozygous LoFs: 1635
Defined: 125747
p: 0.00667

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.12	369	435	0.849	0.0000249	4775
Missense (PolyPhen)		118	165.53	0.71287		1893
Synonymous	-0.838	187	173	1.08	0.00000950	1613
Loss of Function	2.12	24	38.1	0.630	0.00000234	372

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00080	0.00080	rare
Latino/Admixed American	0.046	0.046	notable
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00098	0.00098	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00039	0.00033	rare
South Asian	0.00013	0.00013	rare
Other	0.0074	0.0072	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Acts as a transcriptional repressor through interaction with histone deacetylases (HDACs). May be important for spermiogenesis. {ECO:0000250|UniProtKB:Q8C0R7, ECO:0000303|PubMed:24431330}.;
Disease: DISEASE: Spermatogenic failure 14 (SPGF14) [MIM:615842]: A disorder resulting in the absence (azoospermia) or reduction (oligozoospermia) of sperm in the semen, leading to male infertility. {ECO:0000269|PubMed:24431330}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Intolerance Scores

LoFtool: 0.925
RVIS EVS: -0.95
RVIS percentile EVS: 9.27

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.0482

Gene Damage Prediction

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