DMAC2L

Summary

DMAC2L (distal membrane arm assembly component 2 like, HGNC:18799) is a protein-coding gene on chromosome 14q21.3, encoding ATP synthase subunit s, mitochondrial (Q99766). Involved in regulation of mitochondrial membrane ATP synthase.

This gene encodes a subunit of mitochondrial ATP synthase. Mitochondrial ATP synthase catalyzes ATP synthesis, utilizing an electrochemical gradient of protons across the inner membrane during oxidative phosphorylation. ATP synthase is composed of two linked multi-subunit complexes: the soluble catalytic core, F1, and the membrane-spanning component, Fo, comprising the proton channel. This gene encodes the subunit s, also known as factor B, of the proton channel. This subunit is necessary for the energy transduction activity of the ATP synthase complexes. Alternatively spliced transcript variants encoding different isoforms have been identified.

Source: NCBI Gene 27109 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 65 total — 1 pathogenic, 1 likely-pathogenic
• GTEx eGene: eQTL in 41 tissues, sQTL in 22 (q < 0.05)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.31 (unconstrained)
• MANE Select transcript: NM_001382507
• Notable: 65 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18799
Approved symbol	DMAC2L
Name	distal membrane arm assembly component 2 like
Location	14q21.3
Locus type	gene with protein product
Status	Approved
Aliases	HSU79253, ATPW
Ensembl gene	ENSG00000125375
Ensembl biotype	protein_coding
OMIM	618579
Entrez	27109

Gene structure

Transcript identifiers

Ensembl transcripts: 37 — 32 protein_coding, 3 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined, 1 retained_intron

MANE Select: ENST00000557421

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 5, TSL 2: 2, TSL 3: 3, TSL 5: 1

ENST00000557421, ENST00000245448, ENST00000311459, ENST00000358473, ENST00000426751, ENST00000553774, ENST00000554204, ENST00000554438, ENST00000554951, ENST00000555939, ENST00000556962, ENST00000672419, ENST00000672910, ENST00000904299, ENST00000904300, ENST00000904301, ENST00000929463, ENST00000929464, ENST00000929465, ENST00000992705, ENST00000992706, ENST00001051909, ENST00001059430, ENST00001059431, ENST00001105260, ENST00001105261, ENST00001105262, ENST00001105263, ENST00001106859, ENST00001121757, ENST00001121758, ENST00001121759, ENST00001121760, ENST00001128054, ENST00001130508, ENST00001130509, ENST00001133372

RefSeq mRNA: 7 — MANE Select: NM_001382507 NM_001003803, NM_001003805, NM_001370605, NM_001382507, NM_001382509, NM_001382510, NM_015684

CCDS: CCDS32075, CCDS32076, CCDS45102

Canonical transcript exons

ENST00000557421 — 6 exons

Exon	Start	End
ENSE00002465857	50325609	50327957
ENSE00002469347	50312324	50312389
ENSE00002496144	50314591	50314626
ENSE00003502536	50323945	50324116
ENSE00003603634	50322511	50322719
ENSE00003814712	50321483	50321594

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 95.31.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.6762 / max 75.1101, expressed in 1748 samples.

Highest expression (Bgee): sperm, uterine tube, male germ cell, skeletal muscle tissue of biceps brachii, biceps brachii.

Genetic regulation across tissues (GTEx eQTL / sQTL)

DMAC2L is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 41 tissues and its splicing (sQTL) in 22 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 63 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Heart Atrial Appendage	eqtl	5.2e-72	-0.66	14:50322323:C:T
Testis	sqtl	2.0e-69	+1.14	14:50312098:A:C
Muscle Skeletal	eqtl	6.0e-57	-0.39	14:50312098:A:C
Heart Left Ventricle	eqtl	2.1e-54	-0.45	14:50312098:A:C
Esophagus Muscularis	eqtl	1.3e-30	-0.39	14:50312098:A:C
Colon Transverse	eqtl	1.8e-21	-0.31	14:50317180:G:T
Esophagus Gastroesophageal Junction	eqtl	1.6e-20	-0.42	14:50322323:C:T
Skin Sun Exposed Lower leg	eqtl	9.1e-20	-0.24	14:50312098:A:C
Testis	eqtl	3.6e-18	-0.20	14:50318201:C:A
Muscle Skeletal	sqtl	1.2e-17	+1.72	14:50312363:G:GCTCCCTCCCTCC
Colon Sigmoid	eqtl	2.5e-17	-0.31	14:50322383:A:AATAC
Thyroid	eqtl	6.3e-16	-0.24	14:50317093:A:G
Stomach	eqtl	1.1e-12	-0.23	14:50322323:C:T
Artery Tibial	eqtl	3.7e-12	-0.24	14:50322383:A:AATAC
Adipose Visceral Omentum	eqtl	5.8e-12	-0.16	14:50317180:G:T
Cells Cultured fibroblasts	eqtl	9.1e-12	-1.08	14:50312363:G:GCTCCCTCCCTCC
Adipose Subcutaneous	eqtl	2.2e-11	-0.17	14:50318201:C:A
Brain Frontal Cortex BA9	eqtl	1.4e-10	-0.35	14:50340005:G:A
Skin Not Sun Exposed Suprapubic	eqtl	3.2e-10	-0.19	14:50309523:C:T
Esophagus Mucosa	eqtl	7.6e-10	-0.16	14:50321495:C:T

FANTOM5 promoters

3 alternative TSS:

Promoter ID	TPM avg	Samples expressed
139489	5.8255	1683
139490	1.8359	1037
139488	0.0148	5

Top tissues by expression

showing 100 of 297 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	95.31	gold quality
right uterine tube	UBERON:0001302	94.19	gold quality
male germ cell	CL:0000015	93.58	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	93.24	gold quality
biceps brachii	UBERON:0001507	93.18	gold quality
endothelial cell	CL:0000115	92.58	gold quality
triceps brachii	UBERON:0001509	92.56	gold quality
gluteal muscle	UBERON:0002000	91.28	gold quality
oocyte	CL:0000023	91.25	gold quality
diaphragm	UBERON:0001103	90.93	gold quality
adult organism	UBERON:0007023	90.90	gold quality
heart right ventricle	UBERON:0002080	89.88	gold quality
upper leg skin	UBERON:0004262	89.88	gold quality
right testis	UBERON:0004534	89.71	gold quality
penis	UBERON:0000989	89.70	gold quality
left testis	UBERON:0004533	89.67	gold quality
muscle of leg	UBERON:0001383	89.61	gold quality
gastrocnemius	UBERON:0001388	89.58	gold quality
muscle organ	UBERON:0001630	89.40	gold quality
vastus lateralis	UBERON:0001379	89.18	gold quality
endometrium epithelium	UBERON:0004811	88.98	gold quality
oral cavity	UBERON:0000167	88.83	gold quality
testis	UBERON:0000473	88.66	gold quality
monocyte	CL:0000576	88.62	gold quality
skeletal muscle tissue	UBERON:0001134	88.62	gold quality
mononuclear cell	CL:0000842	88.54	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	88.44	gold quality
quadriceps femoris	UBERON:0001377	88.37	gold quality
leukocyte	CL:0000738	88.08	gold quality
skin of hip	UBERON:0001554	87.78	gold quality
ectocervix	UBERON:0012249	87.72	gold quality
esophagus squamous epithelium	UBERON:0006920	87.39	gold quality
endocervix	UBERON:0000458	87.25	gold quality
pigmented layer of retina	UBERON:0001782	87.20	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	87.16	gold quality
body of uterus	UBERON:0009853	87.08	gold quality
hindlimb stylopod muscle	UBERON:0004252	86.80	gold quality
spinal cord	UBERON:0002240	86.77	gold quality
epithelium of esophagus	UBERON:0001976	86.73	gold quality
jejunum	UBERON:0002115	86.64	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.63	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.53	gold quality
metanephros cortex	UBERON:0010533	86.39	gold quality
jejunal mucosa	UBERON:0000399	86.37	gold quality
nipple	UBERON:0002030	86.07	gold quality
secondary oocyte	CL:0000655	86.06	gold quality
rectum	UBERON:0001052	85.93	gold quality
muscle tissue	UBERON:0002385	85.89	gold quality
eye	UBERON:0000970	85.80	gold quality
prefrontal cortex	UBERON:0000451	85.48	gold quality
palpebral conjunctiva	UBERON:0001812	85.35	gold quality
corpus callosum	UBERON:0002336	85.33	gold quality
left lobe of thyroid gland	UBERON:0001120	85.21	gold quality
muscle layer of sigmoid colon	UBERON:0035805	85.16	gold quality
uterine cervix	UBERON:0000002	85.10	gold quality
adipose tissue	UBERON:0001013	85.10	gold quality
bone marrow	UBERON:0002371	85.10	gold quality
body of tongue	UBERON:0011876	85.03	gold quality
thyroid gland	UBERON:0002046	84.97	gold quality
fallopian tube	UBERON:0003889	84.94	gold quality
right lobe of thyroid gland	UBERON:0001119	84.93	gold quality
connective tissue	UBERON:0002384	84.88	gold quality
squamous epithelium	UBERON:0006914	84.74	gold quality
ventral tegmental area	UBERON:0002691	84.73	gold quality
cardiac ventricle	UBERON:0002082	84.50	gold quality
superficial temporal artery	UBERON:0001614	84.44	gold quality
heart left ventricle	UBERON:0002084	84.41	gold quality
calcaneal tendon	UBERON:0003701	84.39	gold quality
body of pancreas	UBERON:0001150	84.38	gold quality
Brodmann (1909) area 9	UBERON:0013540	84.33	gold quality
amygdala	UBERON:0001876	84.32	gold quality
corpus epididymis	UBERON:0004359	84.30	gold quality
subcutaneous adipose tissue	UBERON:0002190	84.28	gold quality
sigmoid colon	UBERON:0001159	84.24	gold quality
adult mammalian kidney	UBERON:0000082	84.18	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	84.17	gold quality
mammalian vulva	UBERON:0000997	84.12	gold quality
uterus	UBERON:0000995	84.09	gold quality
esophagus mucosa	UBERON:0002469	84.06	gold quality
mucosa of transverse colon	UBERON:0004991	84.05	gold quality
left ovary	UBERON:0002119	84.02	gold quality
medial globus pallidus	UBERON:0002477	84.01	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	84.01	gold quality
oviduct epithelium	UBERON:0004804	83.99	gold quality
pharyngeal mucosa	UBERON:0000355	83.97	gold quality
zone of skin	UBERON:0000014	83.93	gold quality
cingulate cortex	UBERON:0003027	83.91	gold quality
duodenum	UBERON:0002114	83.90	gold quality
midbrain	UBERON:0001891	83.89	gold quality
substantia nigra	UBERON:0002038	83.88	gold quality
subthalamic nucleus	UBERON:0001906	83.82	gold quality
deltoid	UBERON:0001476	83.77	gold quality
endometrium	UBERON:0001295	83.76	gold quality
anterior cingulate cortex	UBERON:0009835	83.76	gold quality
right frontal lobe	UBERON:0002810	83.68	gold quality
adrenal tissue	UBERON:0018303	83.66	gold quality
inferior vagus X ganglion	UBERON:0005363	83.59	gold quality
large intestine	UBERON:0000059	83.57	gold quality
transverse colon	UBERON:0001157	83.53	gold quality
colon	UBERON:0001155	83.52	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.60

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 76 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM
Frontal cortex	tissue	30.0
Nucleus accumbens	tissue	23.1
Caudate putamen	tissue	22.2
Locus coeruleus	tissue	21.6
Hippocampus	tissue	21.1
Skeletal muscle	tissue	20.8
Postcentral gyrus	tissue	20.6
Choroid plexus	tissue	17.7
Tongue	tissue	17.2
Testis	tissue	15.9
Corpus callosum	tissue	14.8
Heart muscle	tissue	14.0
Spinal cord	tissue	14.0
Thyroid gland	tissue	13.5
Bone marrow	tissue	13.3
Medulla oblongata	tissue	12.9
Skin 1	tissue	12.4
Midbrain	tissue	12.4
Parathyroid gland	tissue	11.7
Breast	tissue	11.1
Thalamus	tissue	10.9
Pons	tissue	10.8
Retina	tissue	10.6
Substantia nigra	tissue	10.4
Esophagus	tissue	10.2
Periaqueductal gray	tissue	10.0
Adipose tissue	tissue	9.8
Lymph node	tissue	9.7
Superior colliculi	tissue	9.7
Liver	tissue	9.7
Pancreas	tissue	9.4
Duodenum	tissue	9.4
Stomach 1	tissue	8.8
Amygdala	tissue	8.8
Putamen	tissue	8.7
Hypothalamus	tissue	8.7
Small intestine	tissue	8.5
Septum	tissue	8.5
Ventral forebrain	tissue	8.4
Salivary gland	tissue	8.3
Epididymis	tissue	8.3
Hippocampal formation	tissue	8.3
Tonsil	tissue	8.1
Cerebral cortex	tissue	7.9
Rectum	tissue	7.9
Colon	tissue	7.9
Kidney	tissue	7.9
Somatosensory cortex	tissue	7.9
Temporal cortex	tissue	7.9
Occipital cortex	tissue	7.8
Prostate	tissue	7.7
Motor cortex	tissue	7.5
Entorhinal cortex	tissue	7.4
Fallopian tube	tissue	7.4
Urinary bladder	tissue	7.3
Retrosplenial and cingulate cortex	tissue	7.3
Retrosplenial cortex	tissue	7.3
Prefrontal cortex	tissue	7.2
Thymus	tissue	6.9
Basal ganglia	tissue	6.7

Brain sub-regions (HPA Brain Atlas): detected in 189; highest nTPM — Parieto-temporal junction (white matter) (35.7), Temporal white matter (33.5), Corpus callosum, splenium (white matter) (32.1), Corpus callosum, genu (white matter) (31.2), Dorsal funiculus (white matter) (30.0).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYC

miRNA regulators (miRDB)

Targeting DMAC2L by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

13 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-1290	99.59	69.90	2079
HSA-MIR-4721	99.26	66.05	818
HSA-MIR-3922-5P	98.77	66.53	1059
HSA-MIR-921	97.09	66.45	562
HSA-MIR-4662A-3P	97.02	67.77	941
HSA-MIR-514A-3P	96.43	67.77	1048
HSA-MIR-514B-3P	96.43	67.77	1048
HSA-MIR-10525-3P	96.32	68.04	699
HSA-MIR-1291	96.28	65.89	1224
HSA-MIR-6775-3P	95.76	65.91	982

Functional genomics

gnomAD constraint: pLI 4.8e-07, LOEUF 1.31, missense Z 0.515 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000557421 — one region, missense o/e 0.97.

Literature-anchored findings (GeneRIF, showing 1)

• The study is the first to show that ATP5S is one of the target genes of miR-34a. (PMID:26385595)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	dmac2l	ENSDARG00000012072
mus_musculus	Dmac2l	ENSMUSG00000054894
rattus_norvegicus	Dmac2l	ENSRNOG00000004893
drosophila_melanogaster	CG10731	FBGN0034081
caenorhabditis_elegans		WBGENE00015460
caenorhabditis_elegans		WBGENE00050937

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1915305) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 1 distinct phenotype terms.

Mouse phenotype (MP)	Records
narrow eye opening	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Pongo abelii	Q5R9E6	99.0%	Diamond
Macaca fascicularis	Q4R5S4	93.0%	Diamond
Bos taurus	P22027	90.5%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
MIR4504	ncRNA	100616261
MAP4K5	protein-coding	11183
ATL1	protein-coding	51062
L2HGDH	protein-coding	79944
CDKL1	protein-coding	8814
LINC01599	ncRNA	196913
SOS2	protein-coding	6655
VCPKMT	protein-coding	79609
SAV1	protein-coding	60485

Protein

Protein identifiers

ATP synthase subunit s, mitochondrial — Q99766 (reviewed: Q99766)

Alternative names: ATP synthase-coupling factor B, Distal membrane arm assembly complex 2-like protein, Mitochondrial ATP synthase regulatory component factor B

All UniProt accessions (5): A0A5F9ZGZ2, A0A5K1VW82, A0A8I5KUF2, Q99766, G3V467

UniProt curated annotations — full annotation on UniProt →

Function. Involved in regulation of mitochondrial membrane ATP synthase. Necessary for H(+) conduction of ATP synthase. Facilitates energy-driven catalysis of ATP synthesis by blocking a proton leak through an alternative proton exit pathway.

Subunit / interactions. Homotetramer. Associates with ATP synthase.

Subcellular location. Mitochondrion. Mitochondrion inner membrane.

Similarity. Belongs to the ATP synthase subunit s family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q99766-1	1	yes
Q99766-2	2
Q99766-3	3

RefSeq proteins (7): NP_001003803, NP_001003805, NP_001357534, NP_001369436, NP_001369438, NP_001369439, NP_056499 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR032675	LRR_dom_sf	Homologous_superfamily

UniProt features (14 total): splice variant 4, repeat 4, binding site 2, transit peptide 1, chain 1, sequence variant 1, region of interest 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q99766-F1	91.27	0.85

Human Protein Atlas

Protein class: Predicted intracellular proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): mitochondria; nucleoplasm

Antibody reliability (HPA): IF approved

Functional residue map

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

Ligand- & substrate-binding residues (2)

Position	Role
59	Mg(2+)
93	Mg(2+)

Function

Pathways and Gene Ontology

Reactome pathways

2 curated (TAS) of 6; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

6 pathways:

ID	Pathway	Evidence
R-HSA-8949613	Cristae formation	curated
R-HSA-163210	Formation of ATP by chemiosmotic coupling	curated
R-HSA-1428517	Aerobic respiration and respiratory electron transport	—
R-HSA-1430728	Metabolism	—
R-HSA-1592230	Mitochondrial biogenesis	—
R-HSA-1852241	Organelle biogenesis and maintenance	—

MSigDB gene sets: 147 (showing top): GRUETZMANN_PANCREATIC_CANCER_DN, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_NUCLEOSIDE_PHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, REACTOME_FORMATION_OF_ATP_BY_CHEMIOSMOTIC_COUPLING, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_MONOATOMIC_CATION_TRANSPORT, PUJANA_CHEK2_PCC_NETWORK, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, BROWNE_HCMV_INFECTION_48HR_DN, GOBP_ATP_BIOSYNTHETIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_BIOSYNTHETIC_PROCESS, GOBP_NUCLEOSIDE_TRIPHOSPHATE_METABOLIC_PROCESS, GOBP_NUCLEOSIDE_TRIPHOSPHATE_BIOSYNTHETIC_PROCESS, BROWNE_HCMV_INFECTION_14HR_DN

GO Biological Process (3): ATP biosynthetic process (GO:0006754), proton transmembrane transport (GO:1902600), monoatomic ion transport (GO:0006811)

GO Molecular Function (3): proton transmembrane transporter activity (GO:0015078), metal ion binding (GO:0046872), protein binding (GO:0005515)

GO Cellular Component (4): cytoplasm (GO:0005737), mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), proton-transporting ATP synthase complex (GO:0045259)

Reactome top-level categories

4 top-level categories:

Category	Pathways
Aerobic respiration and respiratory electron transport	1
Mitochondrial biogenesis	1
Metabolism	1
Organelle biogenesis and maintenance	1

GO top-level categories

20 GO namespaces:

Category	Terms
nucleoside triphosphate biosynthetic process	1
purine ribonucleotide biosynthetic process	1
purine ribonucleoside triphosphate biosynthetic process	1
ATP metabolic process	1
monoatomic cation transmembrane transport	1
transport	1
monoatomic cation transmembrane transporter activity	1
proton transmembrane transport	1
cation binding	1
binding	1
intracellular anatomical structure	1
cellular anatomical structure	1
cytoplasm	1
intracellular membrane-bounded organelle	1
organelle inner membrane	1
mitochondrial membrane	1
proton-transporting two-sector ATPase complex	1
cation channel complex	1
respiratory chain complex	1
catalytic complex	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 1 of 10 annotations. The rest are phylogenetic / computational / electronic (IEA).

1 experimentally-supported GO terms:

GO term	NS	Evidence
mitochondrion	CC	high-throughput

Protein interactions and networks

STRING

showing 16 of 898 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DMAC2L	ATP5PD	O75947	577
DMAC2L	ATP5MC3	P48201	540
DMAC2L	ATP5MC1	P05496	534
DMAC2L	ATP5F1B	P06576	489
DMAC2L	ATP5F1C	P36542	489
DMAC2L	COX7A2	P14406	463
DMAC2L	OXA1L	Q15070	433
DMAC2L	COQ4	Q9Y3A0	422
DMAC2L	ATP5ME	P56385	421
DMAC2L	NDUFA1	O15239	413
DMAC2L	ATP5PB	P24539	401
DMAC2L	ATP5MC2	Q06055	389
DMAC2L	ATP5MF	P56134	388
DMAC2L	ATP6V1H	Q9UI12	377
DMAC2L	COQ8A	Q8NI60	370
DMAC2L	DMRT2	Q9Y5R5	370

Disease & clinical

Genetic variants

Variant evidence for DMAC2L: 65 ClinVar records (2 pathogenic / likely pathogenic); 1 GWAS association. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	1
Uncertain significance	36
Likely benign	19
Benign	0

Top pathogenic / likely-pathogenic (2)

Showing all 2 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
1342871	NM_024884.3(L2HGDH):c.1A>G (p.Met1Val)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
2573619	NM_024884.3(L2HGDH):c.140+2_140+8del	Likely pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore DMAC2L’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 22 predictions of 639):

Position(s)	Effect	Δscore	Sites
14:50322502	acceptor_gain	1.0000
14:50322507	acceptor_gain	1.0000
14:50322509–50322510	acceptor_loss	1.0000	4
14:50322510	acceptor_gain	1.0000
14:50322508	acceptor_gain	0.9900
14:50322509	acceptor_loss	0.9900
14:50322720–50322721	donor_loss	0.9900	6
14:50314311	acceptor_gain	0.9800
14:50322722	donor_loss	0.9800	2
14:50312390–50312391	donor_loss	0.9700	4

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

1 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	6.27e-08

Disease associations

OMIM: gene MIM:618579 | disease phenotypes: MIM:236792

GenCC curated gene-disease

Mondo (1): L-2-hydroxyglutaric aciduria (MONDO:0009370)

Orphanet (1): L-2-hydroxyglutaric aciduria (Orphanet:79314)

GWAS associations

1 associations:

Study	Trait	p-value
GCST002312_10	Periodontal disease-related phenotype (Socransky)	8e-6

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

36 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression	4
entinostat	decreases expression, affects cotreatment	2
Acetaminophen	increases expression	2
Estradiol	increases expression, affects cotreatment, decreases expression	2
Smoke	decreases expression	2
GSK-J4	decreases expression	1
dicrotophos	decreases expression	1
urushiol	increases expression	1
methylmercuric chloride	decreases expression	1
glycidyl methacrylate	decreases expression	1
trichostatin A	decreases expression	1
sulforaphane	decreases expression	1
sodium arsenite	affects cotreatment, decreases expression, increases abundance	1
cobaltous chloride	decreases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
beta-methylcholine	affects expression	1
K 7174	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
NSC 689534	affects binding, decreases expression	1
Irinotecan	decreases expression	1
Sunitinib	increases expression	1
Vorinostat	decreases expression	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Copper	affects binding, decreases expression	1
Coumestrol	decreases expression	1
Doxorubicin	decreases expression	1
Formaldehyde	decreases expression	1
Isoniazid	increases expression	1
Manganese	increases abundance, affects cotreatment, decreases expression	1

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.