MDGA2

protein-coding

MAM domain containing glycosylphosphatidylinositol anchor 2, the group of I-set domain containing

Gene summary

Predicted to be involved in regulation of synapse organization and spinal cord motor neuron differentiation. Predicted to act upstream of or within several processes, including motor behavior; negative regulation of neuron apoptotic process; and neuron migration. Predicted to be located in extracellular region and plasma membrane. Predicted to be active in GABA-ergic synapse; glutamatergic synapse; and postsynaptic density membrane. [provided by Alliance of Genome Resources, Jul 2025]

Previous symbols:

MAMDC1

MANE transcript

NM_001113498.3

Inheritance

ClinVar variants

P:7U:41B:5

Top phenotype

DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY 122

gnomAD constraint

pLI —, LoF o/e 0.1

Max pathogenic AF

—

Genomic locus

chr14:46,840,092-47,675,605

External References & Databases

Ensembl (ENSG00000139915)

Transcript & Mutation Effects

hg38 • Region Span ~835.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

developmental and epileptic encephalopathyMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0100620

Submitter: G2P

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to MDGA2 variants in ClinVar

7 Conditions Cataloged

not specifiedTotal: 33

not providedTotal: 6

DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY 122Total: 6

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

MDGA2-related intellectual disabilityTotal: 1

ADNP-related multiple congenital anomalies - intellectual disability - autism spectrum disorderTotal: 1

Intellectual disabilityTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001113498.3. 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			2 clinvar	1 clinvar	1 clinvar	4
missense			35 clinvar	1 clinvar	2 clinvar	38
nonsense	2 clinvar		1 clinvar			3
start loss						0
frameshift	2 clinvar	1 clinvar				3
splice donor/acceptor (+/-2bp)	2 clinvar		3 clinvar			5
Total	6	1	41	2	3	53

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 19 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001113498.3	RefSeq	NP_001106970.4	17	MANE Select
ENST00000399232.8	Ensembl	ENSP00000382178.4	17	MANE Select
NM_182830.4	RefSeq	NP_878250.2	13	Standard
ENST00000357362.7	Ensembl	ENSP00000349925.3	13	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
mdga2a	Danio rerio	Structure: trigeminal motor nucleus Quality: mislocalised abnormal

Gene / Model

Organism

Observed Phenotype

mdga2a

Danio rerio

Structure: trigeminal motor nucleus

Quality: mislocalised

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Post-translational modification: synthesis of GPI-anchored proteins
Post-translational protein modification
Metabolism of proteins

Biological Process

spinal cord motor neuron differentiation

Cellular Component

extracellular region
plasma membrane
anchored component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000426342
Coding exons: 13
Length: 835332
Individuals with no LoFs: 124784
Homozygous LoFs: 0
Heterozygous LoFs: 7
Defined: 124791
p: 0.0000280

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.68	306	400	0.764	0.0000211	4724
Missense (PolyPhen)		78	165.25	0.47202		1923
Synonymous	0.830	125	137	0.910	0.00000720	1413
Loss of Function	5.14	4	38.3	0.104	0.00000209	453

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000035	0.000035	rare
South Asian	0.000033	0.000033	rare
Other	0.00017	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May be involved in cell-cell interactions. {ECO:0000250}.;

Recessive Scores

pRec: 0.112

Intolerance Scores

LoFtool: 0.260
RVIS EVS: -1.02
RVIS percentile EVS: 8.1

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.0524

Gene Damage Prediction

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