MDH1B

protein-coding

malate dehydrogenase 1B

Gene summary

Predicted to enable L-malate dehydrogenase (NAD+) activity. Predicted to be involved in NAD+ metabolic process; dicarboxylic acid metabolic process; and tricarboxylic acid cycle. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_001039845.3

Inheritance

—

ClinVar variants

U:80B:7

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.83

Max pathogenic AF

—

Genomic locus

chr2:206,737,763-206,765,328

External References & Databases

Ensembl (ENSG00000138400)

Transcript & Mutation Effects

hg38 • Region Span ~27.6 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to MDH1B variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 81

not providedTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001039845.3. 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	1 clinvar		2
missense			76 clinvar	5 clinvar		81
nonsense			1 clinvar			1
start loss			1 clinvar			1
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar	1 clinvar		2
Total	0	0	80	7	0	87

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 18 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001039845.3	RefSeq	NP_001034934.1	12	MANE Select
ENST00000374412.8	Ensembl	ENSP00000363533.3	12	MANE Select
NM_001282940.2	RefSeq	NP_001269869.1	12	Standard
NM_001330223.2	RefSeq	NP_001317152.1	9	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

carbohydrate metabolic process
tricarboxylic acid cycle
oxaloacetate metabolic process
malate metabolic process
NADH metabolic process

Molecular Function

L-malate dehydrogenase activity

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000374412
Coding exons: 12
Length: 27785
Individuals with no LoFs: 125683
Homozygous LoFs: 0
Heterozygous LoFs: 65
Defined: 125748
p: 0.000258

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.448	264	285	0.925	0.0000147	3398
Missense (PolyPhen)		57	59.954	0.95073		755
Synonymous	0.197	100	103	0.975	0.00000560	982
Loss of Function	0.823	23	27.7	0.831	0.00000134	334

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00055	0.00055	rare
Latino/Admixed American	0.00017	0.00017	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00016	0.00016	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00032	0.00026	rare
South Asian	0.00049	0.00049	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.0916

Intolerance Scores

LoFtool: 0.924
RVIS EVS: -0.11
RVIS percentile EVS: 45.49

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.324

Gene Damage Prediction

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