MAMDC4

protein-coding

MAM domain containing 4

Gene summary

Predicted to enable protein histidine phosphatase activity. Predicted to be involved in nervous system development. Predicted to act upstream of or within Wnt signaling pathway and protein localization to nucleus. Predicted to be located in cytosol. Predicted to be part of Wnt signalosome. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_206920.3

Inheritance

—

ClinVar variants

U:262B:21

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 1.09

Max pathogenic AF

—

Genomic locus

chr9:136,850,943-136,860,799

External References & Databases

Ensembl (ENSG00000177943)

Transcript & Mutation Effects

hg38 • Region Span ~9.9 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

schizophreniaNO_KNOWN

Inheritance Pattern: Unknown

Disease ID:MONDO:0005090

Submitter: Labcorp Genetics (formerly Invitae)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to MAMDC4 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 261

not providedTotal: 7

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_206920.3. 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			4 clinvar	5 clinvar		9
missense			251 clinvar	16 clinvar		267
nonsense			2 clinvar			2
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			5 clinvar			5
Total	0	0	262	21	0	283

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_206920.3	RefSeq	NP_996803.2	27	MANE Select
ENST00000317446.7	Ensembl	ENSP00000319388.2	27	MANE Select
ENST00000445819.5	Ensembl	ENSP00000411339.1	29	Standard
ENST00000445819.6	Ensembl	ENSP00000411339.1	29	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

protein transport

Cellular Component

integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000317446
Coding exons: 27
Length: 9855
Individuals with no LoFs: 122153
Homozygous LoFs: 24
Heterozygous LoFs: 3421
Defined: 125598
p: 0.0138

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.841	756	694	1.09	0.0000444	7177
Missense (PolyPhen)		307	270.33	1.1356		3078
Synonymous	-3.02	375	308	1.22	0.0000209	2407
Loss of Function	-0.710	74	67.7	1.09	0.00000363	642

Population LoF Frequency

Population	CAF	p-value	Status
African	0.013	0.013	notable
Latino/Admixed American	0.0073	0.0072	notable
Ashkenazi Jewish	0.0061	0.0061	notable
East Asian	0.0020	0.0019	notable
Finnish	0.024	0.024	notable
European (Non-Finnish)	0.019	0.019	notable
South Asian	0.0056	0.0055	notable
Other	0.016	0.016	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Probably involved in the sorting and selective transport of receptors and ligands across polarized epithelia. {ECO:0000250|UniProtKB:Q63191}.;

Recessive Scores

pRec: 0.100

Intolerance Scores

LoFtool: 0.979
RVIS EVS: 1.89
RVIS percentile EVS: 97.28

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.146

Gene Damage Prediction

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