MLDHR

Summary

MLDHR (mitochondrial lactate dehydrogenase regulator, HGNC:55481) is a protein-coding gene on chromosome 10q23.31, encoding PTEN upstream open reading frame MP31 (C0HLV8). Inhibits lactate dehydrogenase (LDH)-mediated conversion of lactate to pyruvate in mitochondria by competing with mitochondrial LDH for binding to NAD(+).

Enables L-lactate dehydrogenase inhibitor activity. Involved in negative regulation of oxidative phosphorylation. Located in mitochondrion.

Source: NCBI Gene 133834869 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 28 total — 1 likely-pathogenic

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:55481
Approved symbol	MLDHR
Name	mitochondrial lactate dehydrogenase regulator
Location	10q23.31
Locus type	gene with protein product
Status	Approved
Aliases	MP31, PTENURF
Ensembl gene	ENSG00000289051
Ensembl biotype	protein_coding
OMIM	620760
Entrez	133834869

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000692337

RefSeq mRNA: 1 — MANE Select: None NM_001433720

Canonical transcript exons

ENST00000692337 — 1 exons

Exon	Start	End
ENSE00003937353	87863559	87863654

Expression profiles

Top tissues by expression

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

Regulation

Is transcription factor: no

Cross-species orthologs

0 orthologs

Protein

Protein identifiers

PTEN upstream open reading frame MP31 — C0HLV8 (reviewed: C0HLV8)

Alternative names: Micropeptide 31, Mitochondrial lactate dehydrogenase regulator

All UniProt accessions (1): C0HLV8

UniProt curated annotations — full annotation on UniProt →

Function. Inhibits lactate dehydrogenase (LDH)-mediated conversion of lactate to pyruvate in mitochondria by competing with mitochondrial LDH for binding to NAD(+). Also inhibits cellular lactate utilization.

Subunit / interactions. Interacts with lactate dehydrogenases LDHA and LDHB; interaction with mitochondrial LDH leads to inhibition of lactate dehydrogenase activity, preventing conversion of lactate to pyruvate.

Subcellular location. Mitochondrion.

Tissue specificity. Expressed in brain (at protein level). Expressed at lower levels in glioblastomas than in normal brain tissue (at protein level).

RefSeq proteins (1): NP_001420649 (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR054159	MP31	Family

Pfam: PF22001

UniProt features (3 total): mutagenesis site 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-C0HLV8-F1	83.86	0.46

Functional residue map

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

Mutagenesis-validated functional residues (2):

Position	Phenotype
5	abolishes interaction with ldha and ldhb.
12	abolishes interaction with ldha and ldhb.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 13 (showing top): GOBP_GENERATION_OF_PRECURSOR_METABOLITES_AND_ENERGY, GOBP_REGULATION_OF_OXIDATIVE_PHOSPHORYLATION, GOBP_OXIDATIVE_PHOSPHORYLATION, GOBP_REGULATION_OF_GENERATION_OF_PRECURSOR_METABOLITES_AND_ENERGY, GOBP_REGULATION_OF_CELLULAR_RESPIRATION, GOBP_CELLULAR_RESPIRATION, GOMF_ENZYME_INHIBITOR_ACTIVITY, GOMF_ENZYME_REGULATOR_ACTIVITY, chr10q23, GOBP_REGULATION_OF_AEROBIC_RESPIRATION, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_RESPIRATION, GOMF_MOLECULAR_FUNCTION_INHIBITOR_ACTIVITY, GOCC_MITOCHONDRION

GO Biological Process (1): negative regulation of oxidative phosphorylation (GO:0090324)

GO Molecular Function (2): L-lactate dehydrogenase inhibitor activity (GO:0160193), protein binding (GO:0005515)

GO Cellular Component (1): mitochondrion (GO:0005739)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of oxidative phosphorylation	1
oxidative phosphorylation	1
negative regulation of cellular respiration	1
L-lactate dehydrogenase (NAD+) activity	1
enzyme inhibitor activity	1
binding	1
cytoplasm	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: A0A023IWD9, A0A023IWE0, A0A023IWE1, A0A023IWG1, A0A023IWG2, A0A023IWI5, A0A023IWI8, A0A023IWK3, A0A023IWK5, A0A023IWM4, A0A023UBX6, A8W7M6, A8W7M9, A8W7N4, A8W7N6, A8W7P0, A8W7P3, C0HJR6, C0HJY2, C0HLV8, C1CZW1, P08061, P0CU63, P0CU64, P0CU65, P0CY02, P0CY03, P0CY04, P0CY05, P0CY77, P0DKT9, P0DQM5, P0DSG8, P13062, P29893, P33581, P55369, P55536, P64872, P83672

Diamond homologs: C0HLV8, C0HLV9

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	26
Likely benign	0
Benign	1

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
3780930	NM_000314.8(PTEN):c.-896T>C	Likely pathogenic

SpliceAI

5 predictions. Top by Δscore:

Variant	Effect	Δscore
10:87863639:G:GT	donor_gain	0.7800
10:87863590:GA:G	donor_gain	0.4100
10:87863609:G:T	donor_gain	0.2400
10:87863609:G:GT	donor_gain	0.2100
10:87863639:G:T	donor_gain	0.2000

AlphaMissense

0 scored. Top likely-pathogenic:

Disease associations

OMIM: gene MIM:620760 | disease phenotypes: MIM:153480, MIM:158350

GenCC curated gene-disease

Mondo (5): Bannayan-Riley-Ruvalcaba syndrome (MONDO:0007924), Cowden disease (MONDO:0016063), PTEN hamartoma tumor syndrome (MONDO:0017623), hereditary neoplastic syndrome (MONDO:0015356), Cowden syndrome 1 (MONDO:0008021)

Orphanet (4): Bannayan-Riley-Ruvalcaba syndrome (Orphanet:109), Cowden syndrome (Orphanet:201), PTEN hamartoma tumor syndrome (Orphanet:306498), Inherited cancer-predisposing syndrome (Orphanet:140162)

HPO phenotypes

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

GWAS associations

0 associations (top):

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D006223	Hamartoma Syndrome, Multiple	C04.445.435; C04.651.435; C04.700.435; C16.320.700.435
D009386	Neoplastic Syndromes, Hereditary	C04.700; C16.320.700

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03306446	PHASE4	UNKNOWN	Changing the coUrse of cRohn’s Disease With an Early Use of Adalimumab
NCT04094675	PHASE2	COMPLETED	Sirolimus for Cowden Syndrome With Colon Polyposis
NCT00971789	PHASE2	COMPLETED	Sirolimus to Treat Cowden Syndrome and Other PTEN Hamartomatous Tumor Syndromes
NCT00620594	PHASE1	COMPLETED	A Phase I/II Study of BEZ235 in Patients With Advanced Solid Malignancies Enriched by Patients With Advanced Breast Cancer
NCT01757964	PHASE1	COMPLETED	Bacteriotherapy in Pediatric Inflammatory Bowel Disease
NCT07218575	PHASE2/PHASE3	NOT_YET_RECRUITING	Double-Blind Trial of Everolimus for Improving Social Abilities in PTEN Germline Mutations
NCT00600275	PHASE1/PHASE2	COMPLETED	A Phase I/II Study of BGT226 in Adult Patients With Advanced Solid Malignancies Including Patients With Advanced Breast Cancer
NCT02856763	Not specified	COMPLETED	Predictive Factors of ANTI-TNF Response in Luminal Crohn’s Disease Complicated by Abscess
NCT03487900	Not specified	UNKNOWN	Is the Endoscopic Remission Evaluation, Using the CREDO 1 Index / Score in CD Patients in Clinical Remission at Baseline, Predictive of Sustained Clinical Remission Using a 2-year Follow up
NCT03498625	Not specified	COMPLETED	Crohn’s Disease Endoscopic REmission Definition in an Objective Way
NCT03702309	Not specified	RECRUITING	Liquid Biopsy Evaluation and Repository Development at Princess Margaret
NCT06163365	Not specified	UNKNOWN	Inherited Cancer Early Diagnosis (ICED) Study
NCT06523582	Not specified	RECRUITING	Genetic Bases of Neuroendocrine Neoplasms in Mexican Patients
NCT02991807	PHASE1/PHASE2	COMPLETED	RAD001 and Neurocognition in PTEN Hamartoma Tumor Syndrome
NCT06080165	PHASE1/PHASE2	WITHDRAWN	Sirolimus for Improving Social Abilities in People With PTEN Germline Mutations
NCT02461446	Not specified	RECRUITING	Natural History Study of Individuals With Autism and Germline Heterozygous PTEN Mutations
NCT03050268	Not specified	RECRUITING	Familial Investigations of Childhood Cancer Predisposition
NCT03630523	Not specified	UNKNOWN	Response of Immune System to Flu Vaccination in PHTS
NCT05671107	Not specified	COMPLETED	Development and Validation of an Online Neurobehavioral Evaluation Tool for PTEN Patients
NCT06462430	Not specified	RECRUITING	PTEN Hamartoma Tumor Syndrome Pediatric Patient Registry
NCT00001496	Not specified	COMPLETED	Establishment of Normal Breast Epithelial Cell Lines From Patients at High Risk for Breast Cancer
NCT00001898	Not specified	COMPLETED	Microarray Analysis for Human Genetic Disease
NCT00026884	Not specified	RECRUITING	Collection of Serum and Tissue Samples From Patients With Biopsy-Proved or Suspected Malignant Disease
NCT02289326	Not specified	COMPLETED	Biomarker Monitoring in TP53 Mutation Carriers
NCT02958462	Not specified	RECRUITING	Pre-myeloid Cancer and Bone Marrow Failure Clinic Study
NCT03160274	Not specified	RECRUITING	Genetic Analysis of Pheochromocytomas, Paragangliomas and Associated Conditions
NCT03426878	Not specified	COMPLETED	Cancer Health Assessments Reaching Many
NCT03857594	Not specified	ACTIVE_NOT_RECRUITING	Integrative Sequencing In Germline and Hereditary Tumours
NCT03973450	Not specified	UNKNOWN	Epidemiology of Pituitary Tumours: Prevalence of Associated Neoplasia
NCT03979612	Not specified	UNKNOWN	Evaluation of the Adhesion to the GENEPY Network
NCT04261972	Not specified	ACTIVE_NOT_RECRUITING	Cell-free DNA in Hereditary And High-Risk Malignancies 1
NCT04494945	Not specified	RECRUITING	Identifying and Caring for Individuals With Inherited Cancer Syndrome
NCT04541654	Not specified	RECRUITING	Li-Fraumeni & TP53 (LiFT UP): Understanding and Progress
NCT04763915	Not specified	ACTIVE_NOT_RECRUITING	Improving Care After Inherited Cancer Testing
NCT05562778	Not specified	RECRUITING	Chatbot to Maximize Hereditary Cancer Genetic Risk Assessment
NCT05664867	Not specified	RECRUITING	Implementation of Population Cancer Genetic Services in Federally Qualified Health Centers (FQHC)
NCT05721326	Not specified	COMPLETED	Sequential EHR Based Interventions to Increase Genetic Testing for Breast and Ovarian Cancer Predisposition
NCT06096688	Not specified	RECRUITING	Discovering New Targets for Colorectal and Endometrial Cancer Risk Reduction
NCT06654466	Not specified	RECRUITING	Closing the GAPS: Guideline Adherence, Prevention and Surveillance in Hereditary Cancer
NCT06708429	Not specified	RECRUITING	Lynch Syndrome X-Talk of Enteral Mucosa With Immune System