LDHD

protein-coding

lactate dehydrogenase D

Gene summary

The protein encoded by this gene belongs to the D-isomer specific 2-hydroxyacid dehydrogenase family. The similar protein in yeast has both D-lactate and D-glycerate dehydrogenase activities. Alternative splicing occurs at this locus and two transcript variants encoding distinct isoforms have been identified. [provided by RefSeq, Jul 2008]

MANE transcript

NM_194436.3

Inheritance

ClinVar variants

P:8U:92B:14

Top phenotype

D-lactic aciduria

gnomAD constraint

pLI —, LoF o/e 0.86

Max pathogenic AF

—

Genomic locus

chr16:75,111,860-75,116,780

External References & Databases

Ensembl (ENSG00000166816)

Transcript & Mutation Effects

hg38 • Region Span ~4.9 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

Clinical Genomic Database (CGD)

D-lactic aciduriaAR

Manifestation: Biochemical; Musculoskeletal; Neurologic; Renal

Intervention: Renal

Rationale: The condition can manifest with gouty arthropathy, and medical (eg, with colchicine and allopurinol) and dietary management (eg, related to meat consumption) has been reported as beneficial

Refs: 30931947; 31638601

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to LDHD variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 92

LDHD-related disorderTotal: 12

Lactic aciduria due to D-lactic acidTotal: 12

not providedTotal: 8

Abnormal circulating lactate dehydrogenase concentrationTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_194436.3. 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			3 clinvar	8 clinvar	2 clinvar	13
missense	3 clinvar	2 clinvar	86 clinvar	1 clinvar	3 clinvar	95
nonsense			1 clinvar			1
start loss						0
frameshift	1 clinvar	1 clinvar	1 clinvar			3
splice donor/acceptor (+/-2bp)	1 clinvar		1 clinvar			2
Total	5	3	92	9	5	114

Highest pathogenic variant AF is 0.00018967899

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 43 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_194436.3	RefSeq	NP_919417.1	11	MANE Select
ENST00000450168.3	Ensembl	ENSP00000417011.2	11	MANE Select
NM_153486.4	RefSeq	NP_705690.2	11	Standard
ENST00000300051.8	Ensembl	ENSP00000300051.4	11	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Pyruvate metabolism - Homo sapiens (human)
Pyruvate Dehydrogenase Complex Deficiency
Primary hyperoxaluria II, PH2
Pyruvate kinase deficiency
Leigh Syndrome

Biological Process

oxidation-reduction process
lactate catabolic process

Molecular Function

D-lactate dehydrogenase (cytochrome) activity
protein binding
D-lactate dehydrogenase activity
flavin adenine dinucleotide binding
FAD binding

Cellular Component

mitochondrion
mitochondrial inner membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000300051
Coding exons: 11
Length: 4912
Individuals with no LoFs: 125640
Homozygous LoFs: 0
Heterozygous LoFs: 106
Defined: 125746
p: 0.000422

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.434	324	347	0.934	0.0000240	3218
Missense (PolyPhen)		102	131.82	0.77379		1216
Synonymous	-1.17	176	157	1.12	0.0000120	1096
Loss of Function	0.681	22	25.7	0.855	0.00000139	251

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00025	0.00025	rare
Latino/Admixed American	0.00020	0.00020	rare
Ashkenazi Jewish	0.0011	0.0011	notable
East Asian	0.00060	0.00060	rare
Finnish	0.00030	0.00028	rare
European (Non-Finnish)	0.00052	0.00051	rare
South Asian	0.00020	0.00020	rare
Other	0.00050	0.00049	rare

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.190

Intolerance Scores

LoFtool: 0.118
RVIS EVS: -0.44
RVIS percentile EVS: 24.46

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.999

Gene Damage Prediction

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