MDH1B

Chr 2

malate dehydrogenase 1B

Also known as: RP11-95H11

NCBI Gene: 130752 ENSG00000138400 UniProt: Q5I0G3

The protein functions as an L-malate dehydrogenase that uses NAD+ as a cofactor and participates in the tricarboxylic acid cycle and cellular energy metabolism. This gene is extremely intolerant to loss-of-function mutations based on constraint metrics, but no established human disease associations have been reported to date. Clinical significance of variants in this gene remains to be determined.

ResearchSummary from RefSeq

Predicted to enable L-malate dehydrogenase (NAD+) activity. Predicted to be involved in NADH metabolic process; dicarboxylic acid metabolic process; and tricarboxylic acid cycle. [provided by Alliance of Genome Resources, Apr 2025]

ResearchGenerating clinical summary…

LOEUF 1.18

Clinical Summary— MDH1B

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

75 VUS of 88 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.18LOEUF

pLI 0.000

Z-score 0.82

OE 0.83 (0.60–1.18)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.45Z-score

OE missense 0.93 (0.84–1.02)

264 obs / 285.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.83 (0.60–1.18)

0≤0.351.4

Missense OE?0.93 (0.84–1.02)

0≤0.61.4

Synonymous OE?0.98

0≤1.21.6

LoF obs/exp: 23 / 27.7Missense obs/exp: 264 / 285.3Syn Z: 0.20

ClinVar Variant Classifications

88 submitted variants in ClinVar

ClinVar

Classification Summary

VUS75

Likely Benign5

Conflicting1

VUS

Likely Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	0	0	0	0	0
VUS	0	75	0	0	75
Likely Benign	0	4	0	1	5
Benign	0	0	0	0	0
Conflicting	—				1
Total	0	79	0	1	81

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

26 pathogenic / likely-pathogenic (of 28) ClinVar copy-number / structural variants overlap MDH1B — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →