LDHAL6A

Summary

LDHAL6A (lactate dehydrogenase A like 6A, HGNC:28335) is a protein-coding gene on chromosome 11p15.1, encoding L-lactate dehydrogenase A-like 6A (Q6ZMR3). Catalyzes the interconversion of L-lactate and pyruvate with nicotinamide adenine dinucleotide NAD(+) as a coenzyme.

Enables L-lactate dehydrogenase activity. Predicted to be involved in lactate metabolic process. Located in cytoplasm.

Source: NCBI Gene 160287 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 62 total
• MANE Select transcript: NM_144972

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28335
Approved symbol	LDHAL6A
Name	lactate dehydrogenase A like 6A
Location	11p15.1
Locus type	gene with protein product
Status	Approved
Aliases	MGC23940, LDH6A
Ensembl gene	ENSG00000166800
Ensembl biotype	protein_coding
OMIM	618928
Entrez	160287

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000280706, ENST00000396213

RefSeq mRNA: 2 — MANE Select: NM_144972 NM_001144071, NM_144972

CCDS: CCDS7841

Canonical transcript exons

ENST00000280706 — 7 exons

Exon	Start	End
ENSE00001106755	18465637	18465810
ENSE00001129211	18476384	18476501
ENSE00001129218	18455856	18456806
ENSE00001150845	18463961	18464078
ENSE00001428073	18478706	18479601
ENSE00001599834	18477620	18477743
ENSE00001663470	18475466	18475639

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 95.50.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1266 / max 29.2177, expressed in 49 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
113341	0.1108	48
113344	0.0079	4
113342	0.0044	3
113343	0.0035	2

Top tissues by expression

228 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	95.50	gold quality
oocyte	CL:0000023	92.27	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.75	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	74.05	gold quality
sperm	CL:0000019	72.61	gold quality
left testis	UBERON:0004533	70.54	gold quality
testis	UBERON:0000473	69.67	gold quality
right testis	UBERON:0004534	68.70	gold quality
cortical plate	UBERON:0005343	63.49	gold quality
adrenal tissue	UBERON:0018303	61.75	gold quality
adult organism	UBERON:0007023	57.68	gold quality
cerebellar hemisphere	UBERON:0002245	56.18	gold quality
cerebellar cortex	UBERON:0002129	56.15	gold quality
right hemisphere of cerebellum	UBERON:0014890	55.55	gold quality
bone marrow cell	CL:0002092	55.48	gold quality
ganglionic eminence	UBERON:0004023	55.24	gold quality
cerebellum	UBERON:0002037	55.15	gold quality
esophagus squamous epithelium	UBERON:0006920	54.37	gold quality
epithelium of nasopharynx	UBERON:0001951	54.26	gold quality
prefrontal cortex	UBERON:0000451	52.29	gold quality
leukocyte	CL:0000738	51.95	silver quality
stromal cell of endometrium	CL:0002255	51.93	silver quality
monocyte	CL:0000576	51.50	silver quality
vermiform appendix	UBERON:0001154	51.01	gold quality
mucosa of stomach	UBERON:0001199	50.60	gold quality
granulocyte	CL:0000094	50.34	silver quality
smooth muscle tissue	UBERON:0001135	50.26	gold quality
caecum	UBERON:0001153	50.09	gold quality
right ovary	UBERON:0002118	49.72	gold quality
calcaneal tendon	UBERON:0003701	48.61	silver quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-MTAB-6386	no	47.13
E-ANND-3	no	3.30

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

33 targeting LDHAL6A, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-6744-5P	99.93	66.82	748
HSA-MIR-383-3P	99.85	65.84	1359
HSA-MIR-6817-3P	99.79	68.35	2126
HSA-MIR-3059-5P	99.70	69.93	2491
HSA-MIR-1283	99.69	72.42	3009
HSA-MIR-6832-5P	99.58	64.82	1132
HSA-MIR-3612	99.45	66.02	1333
HSA-MIR-650	99.45	65.77	1309
HSA-MIR-940	99.37	66.14	2064
HSA-MIR-501-3P	99.33	66.12	651
HSA-MIR-502-3P	99.33	66.12	651
HSA-MIR-6808-5P	99.31	66.23	2150
HSA-MIR-6893-5P	99.31	66.25	2119
HSA-MIR-1253	99.12	67.08	1688
HSA-MIR-138-2-3P	98.91	68.33	1643
HSA-MIR-3124-3P	98.87	68.95	2123
HSA-MIR-519A-2-5P	98.78	71.74	1401
HSA-MIR-520B-5P	98.78	71.74	1401
HSA-MIR-6804-3P	98.72	64.82	852
HSA-MIR-606	98.72	67.34	960
HSA-MIR-4684-5P	98.29	67.99	1650
HSA-MIR-4443	98.02	66.25	1928
HSA-MIR-1278	97.75	67.55	628
HSA-MIR-4678	97.59	68.31	902
HSA-MIR-4800-5P	97.22	65.91	324

Literature-anchored findings (GeneRIF, showing 1)

• expression of LDHAL6A was able to activate transcriptional activities of AP1(PMA) (PMID:18351441)

Cross-species orthologs

0 orthologs

Paralogs (5): LDHB (ENSG00000111716), LDHA (ENSG00000134333), MDH2 (ENSG00000146701), LDHC (ENSG00000166796), LDHAL6B (ENSG00000171989)

Protein

Protein identifiers

L-lactate dehydrogenase A-like 6A — Q6ZMR3 (reviewed: Q6ZMR3)

All UniProt accessions (1): Q6ZMR3

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the interconversion of L-lactate and pyruvate with nicotinamide adenine dinucleotide NAD(+) as a coenzyme. Significantly increases the transcriptional activity of JUN, when overexpressed.

Subcellular location. Cytoplasm.

Tissue specificity. Testis-specific.

Pathway. Fermentation; pyruvate fermentation to lactate; (S)-lactate from pyruvate: step 1/1.

Similarity. Belongs to the LDH/MDH superfamily. LDH family.

RefSeq proteins (2): NP_001137543, NP_659409* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001236	Lactate/malate_DH_N	Domain
IPR001557	L-lactate/malate_DH	Family
IPR011304	L-lactate_DH	Family
IPR015955	Lactate_DH/Glyco_Ohase_4_C	Homologous_superfamily
IPR018177	L-lactate_DH_AS	Active_site
IPR022383	Lactate/malate_DH_C	Domain
IPR036291	NAD(P)-bd_dom_sf	Homologous_superfamily

Pfam: PF00056, PF02866

Catalyzed reactions (Rhea), 1 shown:

• (S)-lactate + NAD(+) = pyruvate + NADH + H(+) (RHEA:23444)

UniProt features (25 total): modified residue 14, binding site 7, initiator methionine 1, chain 1, active site 1, cross-link 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6ZMR3-F1	95.39	0.91

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 193 (proton acceptor)

Ligand- & substrate-binding residues (7): 29–57; 99; 106; 138; 138; 169; 248

Post-translational modifications (15): 2, 5, 5, 57, 81, 118, 118, 232, 239, 243, 309, 318, 318, 322, 57

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-70268	Pyruvate metabolism
R-HSA-1428517	Aerobic respiration and respiratory electron transport
R-HSA-1430728	Metabolism

MSigDB gene sets: 37 (showing top): KEGG_CYSTEINE_AND_METHIONINE_METABOLISM, KEGG_GLYCOLYSIS_GLUCONEOGENESIS, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_ORGANIC_ACID_CATABOLIC_PROCESS, GOBP_ORGANIC_ACID_METABOLIC_PROCESS, GOBP_SMALL_MOLECULE_CATABOLIC_PROCESS, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_CH_OH_GROUP_OF_DONORS, GOBP_MONOCARBOXYLIC_ACID_CATABOLIC_PROCESS, GOBP_PYRUVATE_METABOLIC_PROCESS, REACTOME_PYRUVATE_METABOLISM, GOBP_LACTATE_METABOLIC_PROCESS, ZWANG_CLASS_1_TRANSIENTLY_INDUCED_BY_EGF, GOMF_LACTATE_DEHYDROGENASE_ACTIVITY, MIR6867_5P, MIR519A_2_5P_MIR520B_5P

GO Biological Process (3): lactate metabolic process (GO:0006089), pyruvate catabolic process (GO:0042867), carboxylic acid metabolic process (GO:0019752)

GO Molecular Function (4): L-lactate dehydrogenase (NAD+) activity (GO:0004459), catalytic activity (GO:0003824), oxidoreductase activity (GO:0016491), oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor (GO:0016616)

GO Cellular Component (3): cytoplasm (GO:0005737), mitochondrion (GO:0005739), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Aerobic respiration and respiratory electron transport	1
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
monocarboxylic acid metabolic process	1
pyruvate metabolic process	1
monocarboxylic acid catabolic process	1
oxoacid metabolic process	1
L-2-hydroxycarboxylate dehydrogenase (NAD+) activity	1
L-lactate dehydrogenase activity	1
molecular_function	1
catalytic activity	1
oxidoreductase activity, acting on CH-OH group of donors	1
intracellular anatomical structure	1
cellular anatomical structure	1
cytoplasm	1
intracellular membrane-bounded organelle	1
extracellular vesicle	1

Protein interactions and networks

STRING

2937 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LDHAL6A	PKLR	P11973	775
LDHAL6A	GOT1L1	Q8NHS2	754
LDHAL6A	CKMT1B	P12532	734
LDHAL6A	CS	O75390	733
LDHAL6A	CKMT2	P17540	733
LDHAL6A	PKM	P14618	719
LDHAL6A	CKB	P12277	713
LDHAL6A	GOT1	P17174	703
LDHAL6A	CKM	P06732	685
LDHAL6A	GAPDH	P00354	659
LDHAL6A	GGT6	Q6P531	633
LDHAL6A	H6PD	O95479	625
LDHAL6A	GGT7	Q9UJ14	624
LDHAL6A	ALPG	P10696	618
LDHAL6A	GOT2	P00505	609

IntAct

26 interactions, top by confidence:

A	B	Type	Score
LDHC	LDHA	psi-mi:“MI:0914”(association)	0.770
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
CFTR	HAX1	psi-mi:“MI:0914”(association)	0.610
LDHAL6A	CLTCL1	psi-mi:“MI:0915”(physical association)	0.400
DLD	NFKBIE	psi-mi:“MI:0914”(association)	0.350
PDHA1		psi-mi:“MI:0914”(association)	0.350
SDHA	HMGB3	psi-mi:“MI:0914”(association)	0.350
SOD1	NPEPPSL1	psi-mi:“MI:0914”(association)	0.350
SDHA	LMNA	psi-mi:“MI:0914”(association)	0.350
DLD	IRS4	psi-mi:“MI:0914”(association)	0.350
SDHA	NME2P1	psi-mi:“MI:0914”(association)	0.350
FRMD6		psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
IQCB1	PCP4L1	psi-mi:“MI:0914”(association)	0.350
LDHAL6A	LDHA	psi-mi:“MI:0914”(association)	0.350
HTT	NDUFS3	psi-mi:“MI:0914”(association)	0.350
LRRK2	SF3B1	psi-mi:“MI:0914”(association)	0.350

BioGRID (134): ALDH2 (Co-fractionation), ALDH4A1 (Co-fractionation), ARF4 (Co-fractionation), ARF5 (Co-fractionation), CTSD (Co-fractionation), ETFA (Co-fractionation), LDHAL6A (Co-fractionation), LDHAL6A (Co-fractionation), LDHAL6A (Co-fractionation), LDHAL6A (Co-fractionation), LDHAL6A (Co-fractionation), LDHAL6A (Co-fractionation), LDHAL6A (Co-fractionation), LDHAL6A (Co-fractionation), LDHAL6A (Co-fractionation)

ESM2 similar proteins: O13276, O13277, O13278, O93401, O93537, O93538, O93539, O93540, O93541, O93542, O93543, O93544, O93545, O93546, P00341, P00342, P19629, P20373, P33571, P42119, P42120, P42121, P42122, P69080, P69081, P69082, P69083, P69084, P69085, P69086, Q06176, Q1EG91, Q27888, Q29563, Q6DGK2, Q6ZMR3, Q92055, Q95028, Q98SK9, Q98SL1

Diamond homologs: A0A1F3, A5A6N7, A5I1Z6, A7FU32, B1L1N3, C1FMZ1, O13276, O13277, O13278, O93401, O93537, O93538, O93539, O93540, O93541, O93542, O93543, O93544, O93545, O93546, P00336, P00337, P00338, P00339, P00340, P00341, P00342, P04642, P06151, P07195, P07864, P13490, P13491, P13743, P16125, P19629, P19858, P20373, P22988, P22989

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

62 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	50
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1594 predictions. Top by Δscore:

Variant	Effect	Δscore
11:18455978:G:GG	donor_gain	0.9900
11:18456032:A:G	donor_gain	0.9900
11:18456079:G:GG	donor_gain	0.9900
11:18456287:C:G	donor_gain	0.9900
11:18456297:G:GT	donor_gain	0.9900
11:18456807:G:GG	donor_gain	0.9900
11:18476382:A:AG	acceptor_gain	0.9900
11:18476383:G:GG	acceptor_gain	0.9900
11:18477618:A:AG	acceptor_gain	0.9900
11:18477618:AGT:A	acceptor_gain	0.9900
11:18477619:G:GG	acceptor_gain	0.9900
11:18477619:GT:G	acceptor_gain	0.9900
11:18477619:GTG:G	acceptor_gain	0.9900
11:18477739:G:GG	donor_gain	0.9900
11:18456284:GAGC:G	donor_gain	0.9800
11:18475464:A:AG	acceptor_gain	0.9800
11:18475465:G:GG	acceptor_gain	0.9800
11:18476497:TCCAG:T	donor_loss	0.9700
11:18476498:CCAG:C	donor_loss	0.9700
11:18476499:CAGG:C	donor_loss	0.9700
11:18476500:AG:A	donor_loss	0.9700
11:18476501:GG:G	donor_loss	0.9700
11:18476502:G:GC	donor_loss	0.9700
11:18476503:T:C	donor_loss	0.9700
11:18477618:AGTG:A	acceptor_gain	0.9700
11:18477619:GTGG:G	acceptor_gain	0.9700
11:18455954:C:G	donor_gain	0.9600
11:18456163:G:GT	donor_gain	0.9600
11:18456462:T:TA	acceptor_gain	0.9600
11:18475637:GTG:G	donor_gain	0.9600

AlphaMissense

2202 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:18478739:A:C	S290R	0.993
11:18478741:T:A	S290R	0.993
11:18478741:T:G	S290R	0.993
11:18475528:A:C	S161R	0.991
11:18475530:T:A	S161R	0.991
11:18475530:T:G	S161R	0.991
11:18476392:T:A	W201R	0.991
11:18476392:T:C	W201R	0.991
11:18477727:T:A	V273D	0.991
11:18475526:G:A	G160E	0.990
11:18477666:A:C	S253R	0.988
11:18477668:C:A	S253R	0.988
11:18477668:C:G	S253R	0.988
11:18465658:C:T	S89F	0.987
11:18475520:T:A	V158D	0.987
11:18464028:T:C	L65P	0.986
11:18456751:C:A	S24Y	0.985
11:18475532:G:T	G162V	0.985
11:18465774:A:C	S128R	0.984
11:18465776:T:A	S128R	0.984
11:18465776:T:G	S128R	0.984
11:18475532:G:A	G162D	0.984
11:18475525:G:A	G160R	0.983
11:18475525:G:C	G160R	0.983
11:18475536:T:G	C163W	0.983
11:18475553:G:C	R169P	0.982
11:18475619:G:A	G191E	0.982
11:18456751:C:T	S24F	0.981
11:18475468:G:C	D141H	0.980
11:18475526:G:T	G160V	0.980

dbSNP variants (sampled 300 via entrez): RS1000006352 (11:18462834 C>A), RS1000080729 (11:18462044 C>T), RS1000438738 (11:18458713 A>G), RS1000447925 (11:18468357 G>C,T), RS1000555024 (11:18470981 C>A), RS1000794267 (11:18472900 CTT>C), RS1000815425 (11:18470756 G>A,T), RS1000825642 (11:18473089 T>C), RS1001062601 (11:18464139 A>G), RS1001114197 (11:18477067 T>A), RS1001221571 (11:18454290 G>T), RS1001346532 (11:18462556 G>T), RS1001552009 (11:18472344 G>A,T), RS1001666647 (11:18465440 T>A), RS1001804126 (11:18471795 G>A,C,T)

Disease associations

OMIM: gene MIM:618928 | disease phenotypes: MIM:607482, MIM:612124

GenCC curated gene-disease

Mondo (2): dilated cardiomyopathy 1M (MONDO:0011840), hypertrophic cardiomyopathy 12 (MONDO:0012804)

Orphanet (1): Familial isolated dilated cardiomyopathy (Orphanet:154)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C564390	Cardiomyopathy, Dilated, 1M (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

5 total (human), top 5 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol S	decreases methylation	1
theaflavin-3,3’-digallate	affects expression	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Tobacco Smoke Pollution	decreases expression	1
Particulate Matter	increases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.