DMAC2

Summary

DMAC2 (distal membrane arm assembly component 2, HGNC:25496) is a protein-coding gene on chromosome 19q13.2, encoding Distal membrane-arm assembly complex protein 2 (Q9NW81). Required for the assembly of the mitochondrial NADH:ubiquinone oxidoreductase complex (complex I).

Involved in mitochondrial respiratory chain complex I assembly. Located in mitochondrion.

Source: NCBI Gene 55101 — automated summary from GO annotations (Alliance of Genome Resources).

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 65 total
• GTEx eGene: eQTL in 42 tissues, sQTL in 50 (q < 0.05)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.32 (unconstrained)
• MANE Select transcript: NM_018035
• Notable: 65 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25496
Approved symbol	DMAC2
Name	distal membrane arm assembly component 2
Location	19q13.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ10241
Ensembl gene	ENSG00000105341
Ensembl biotype	protein_coding
OMIM	617262
Entrez	55101

Gene structure

Transcript identifiers

Ensembl transcripts: 31 — 16 protein_coding, 12 nonsense_mediated_decay, 3 retained_intron

MANE Select: ENST00000221943

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 2: 10, TSL 3: 1, TSL 4: 2, TSL 5: 1

ENST00000221943, ENST00000301183, ENST00000417807, ENST00000438807, ENST00000586786, ENST00000589102, ENST00000589503, ENST00000589970, ENST00000590641, ENST00000592922, ENST00000594339, ENST00000594660, ENST00000595407, ENST00000595425, ENST00000597457, ENST00000597608, ENST00000979866, ENST00000979867, ENST00000979868, ENST00001048567, ENST00001048568, ENST00001048569, ENST00001048570, ENST00001048571, ENST00001048572, ENST00001048573, ENST00001048574, ENST00001048575, ENST00001060043, ENST00001127015, ENST00001142358

RefSeq mRNA: 11 — MANE Select: NM_018035 NM_001167867, NM_001167868, NM_001167869, NM_001167870, NM_001167871, NM_001320838, NM_001320839, NM_001320840, NM_001320841, NM_001320844, NM_018035

CCDS: CCDS33032, CCDS54269, CCDS54270, CCDS54271, CCDS59389, CCDS59390, CCDS82353, CCDS82354

Canonical transcript exons

ENST00000221943 — 6 exons

Exon	Start	End
ENSE00000708457	41433272	41433434
ENSE00002748963	41431318	41432408
ENSE00003495250	41438218	41438414
ENSE00003574808	41433537	41433673
ENSE00003593721	41436392	41436472
ENSE00003899942	41439882	41439912

Expression profiles

Bgee: expression breadth ubiquitous, 290 present calls, max score 97.58.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 15.9457 / max 175.6751, expressed in 1811 samples.

Highest expression (Bgee): apex of heart, heart left ventricle, cardiac ventricle, jejunal mucosa, parotid gland.

Genetic regulation across tissues (GTEx eQTL / sQTL)

DMAC2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 42 tissues and its splicing (sQTL) in 50 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 92 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Cells Cultured fibroblasts	sqtl	6.0e-263	-1.31	19:41433392:C:G
Muscle Skeletal	sqtl	1.3e-247	-1.28	19:41433392:C:G
Thyroid	sqtl	4.1e-218	-1.27	19:41433392:C:G
Artery Tibial	sqtl	5.6e-217	-1.29	19:41433392:C:G
Esophagus Mucosa	sqtl	5.1e-205	-1.34	19:41433392:C:G
Skin Sun Exposed Lower leg	sqtl	2.9e-187	-1.19	19:41433392:C:G
Nerve Tibial	sqtl	6.6e-175	-1.18	19:41433392:C:G
Adipose Subcutaneous	sqtl	3.1e-169	-1.13	19:41433392:C:G
Adipose Visceral Omentum	sqtl	1.1e-166	-1.18	19:41433392:C:G
Esophagus Muscularis	sqtl	2.2e-160	-1.31	19:41433392:C:G
Heart Atrial Appendage	sqtl	4.7e-160	-1.40	19:41433392:C:G
Skin Not Sun Exposed Suprapubic	sqtl	3.9e-155	-1.22	19:41433392:C:G
Whole Blood	sqtl	1.1e-145	-1.18	19:41433392:C:G
Lung	sqtl	1.3e-145	-1.15	19:41433392:C:G
Cells EBV-transformed lymphocytes	sqtl	8.0e-134	-1.50	19:41433392:C:G
Breast Mammary Tissue	sqtl	2.9e-133	-1.19	19:41433392:C:G
Colon Transverse	sqtl	4.7e-132	-1.26	19:41433392:C:G
Testis	sqtl	3.7e-127	-1.35	19:41433392:C:G
Artery Aorta	sqtl	4.0e-127	-1.23	19:41433392:C:G
Esophagus Gastroesophageal Junction	sqtl	2.4e-111	-1.33	19:41433392:C:G

FANTOM5 promoters

3 alternative TSS:

Promoter ID	TPM avg	Samples expressed
181068	15.3724	1811
181067	0.5408	283
181066	0.0325	9

Top tissues by expression

showing 100 of 292 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	97.58	gold quality
heart left ventricle	UBERON:0002084	97.01	gold quality
cardiac ventricle	UBERON:0002082	96.95	gold quality
jejunal mucosa	UBERON:0000399	95.91	gold quality
parotid gland	UBERON:0001831	95.88	gold quality
heart	UBERON:0000948	95.45	gold quality
right atrium auricular region	UBERON:0006631	94.84	gold quality
left ventricle myocardium	UBERON:0006566	94.78	gold quality
heart right ventricle	UBERON:0002080	94.76	gold quality
duodenum	UBERON:0002114	94.70	gold quality
cardiac atrium	UBERON:0002081	94.64	gold quality
diaphragm	UBERON:0001103	94.38	gold quality
hindlimb stylopod muscle	UBERON:0004252	94.26	gold quality
gastrocnemius	UBERON:0001388	94.22	gold quality
lower esophagus muscularis layer	UBERON:0035833	94.17	gold quality
lower esophagus	UBERON:0013473	94.16	gold quality
biceps brachii	UBERON:0001507	93.98	gold quality
vastus lateralis	UBERON:0001379	93.83	gold quality
muscle of leg	UBERON:0001383	93.80	gold quality
quadriceps femoris	UBERON:0001377	93.75	gold quality
muscle organ	UBERON:0001630	93.70	gold quality
skeletal muscle organ	UBERON:0014892	93.70	gold quality
jejunum	UBERON:0002115	93.46	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	93.46	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	93.45	gold quality
embryo	UBERON:0000922	93.40	gold quality
mucosa of transverse colon	UBERON:0004991	93.29	gold quality
myocardium	UBERON:0002349	93.26	gold quality
muscle layer of sigmoid colon	UBERON:0035805	93.15	gold quality
ganglionic eminence	UBERON:0004023	93.14	gold quality
body of stomach	UBERON:0001161	93.03	gold quality
adult mammalian kidney	UBERON:0000082	92.80	gold quality
skeletal muscle tissue	UBERON:0001134	92.75	gold quality
adult organism	UBERON:0007023	92.70	gold quality
esophagus	UBERON:0001043	92.62	gold quality
small intestine	UBERON:0002108	92.60	gold quality
metanephros cortex	UBERON:0010533	92.49	gold quality
small intestine Peyer’s patch	UBERON:0003454	92.48	gold quality
right lung	UBERON:0002167	92.42	gold quality
muscle tissue	UBERON:0002385	92.39	gold quality
upper lobe of left lung	UBERON:0008952	92.39	gold quality
upper lobe of lung	UBERON:0008948	92.28	gold quality
prefrontal cortex	UBERON:0000451	92.22	gold quality
right adrenal gland	UBERON:0001233	92.15	gold quality
lower esophagus mucosa	UBERON:0035834	92.12	gold quality
transverse colon	UBERON:0001157	92.03	gold quality
metanephros	UBERON:0000081	91.97	gold quality
left coronary artery	UBERON:0001626	91.90	gold quality
cardiac muscle of right atrium	UBERON:0003379	91.85	gold quality
triceps brachii	UBERON:0001509	91.84	gold quality
left adrenal gland	UBERON:0001234	91.82	gold quality
right adrenal gland cortex	UBERON:0035827	91.79	gold quality
nephron tubule	UBERON:0001231	91.78	gold quality
popliteal artery	UBERON:0002250	91.77	gold quality
coronary artery	UBERON:0001621	91.76	gold quality
tibial artery	UBERON:0007610	91.75	gold quality
tongue squamous epithelium	UBERON:0006919	91.74	gold quality
deltoid	UBERON:0001476	91.68	gold quality
left adrenal gland cortex	UBERON:0035825	91.68	gold quality
intestine	UBERON:0000160	91.64	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	91.64	gold quality
esophagus mucosa	UBERON:0002469	91.59	gold quality
colon	UBERON:0001155	91.56	gold quality
kidney	UBERON:0002113	91.55	gold quality
large intestine	UBERON:0000059	91.53	gold quality
body of uterus	UBERON:0009853	91.53	gold quality
cortex of kidney	UBERON:0001225	91.50	gold quality
palpebral conjunctiva	UBERON:0001812	91.43	gold quality
ileal mucosa	UBERON:0000331	91.36	gold quality
ventricular zone	UBERON:0003053	91.35	gold quality
fundus of stomach	UBERON:0001160	91.31	gold quality
aorta	UBERON:0000947	91.30	gold quality
stomach	UBERON:0000945	91.29	gold quality
adrenal cortex	UBERON:0001235	91.22	gold quality
descending thoracic aorta	UBERON:0002345	91.22	gold quality
cervix squamous epithelium	UBERON:0006922	91.21	silver quality
gluteal muscle	UBERON:0002000	91.18	gold quality
right frontal lobe	UBERON:0002810	91.17	gold quality
islet of Langerhans	UBERON:0000006	91.15	gold quality
left uterine tube	UBERON:0001303	91.14	gold quality
mucosa of stomach	UBERON:0001199	91.11	gold quality
right coronary artery	UBERON:0001625	91.11	gold quality
eye	UBERON:0000970	91.03	gold quality
body of pancreas	UBERON:0001150	91.01	gold quality
kidney epithelium	UBERON:0004819	90.97	gold quality
frontal cortex	UBERON:0001870	90.94	gold quality
pancreas	UBERON:0001264	90.88	gold quality
esophagus squamous epithelium	UBERON:0006920	90.84	gold quality
neocortex	UBERON:0001950	90.82	gold quality
squamous epithelium	UBERON:0006914	90.80	gold quality
ectocervix	UBERON:0012249	90.79	gold quality
lung	UBERON:0002048	90.77	gold quality
anterior cingulate cortex	UBERON:0009835	90.76	gold quality
cingulate cortex	UBERON:0003027	90.75	gold quality
thoracic aorta	UBERON:0001515	90.74	gold quality
amniotic fluid	UBERON:0000173	90.70	gold quality
right lobe of thyroid gland	UBERON:0001119	90.63	gold quality
epithelium of esophagus	UBERON:0001976	90.63	gold quality
ascending aorta	UBERON:0001496	90.62	gold quality
saliva-secreting gland	UBERON:0001044	90.61	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	10.07

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Tongue	tissue	74.8
Heart muscle	tissue	72.8	low
Skeletal muscle	tissue	64.1	medium
Corpus callosum	tissue	49.9
Spinal cord	tissue	46.5
Thalamus	tissue	43.9
Cerebral cortex	tissue	43.0	medium
Somatosensory cortex	tissue	43.0
Midbrain	tissue	42.4
Motor cortex	tissue	42.3
Duodenum	tissue	42.3	medium
Superior colliculi	tissue	42.1
Frontal cortex	tissue	41.5
Caudate putamen	tissue	40.9
Medulla oblongata	tissue	40.8
Occipital cortex	tissue	40.3
Small intestine	tissue	40.1	medium
Insular cortex	tissue	38.7
Prefrontal cortex	tissue	38.1
Pons	tissue	37.4
Retrosplenial cortex	tissue	37.3
Substantia nigra	tissue	37.2
Retrosplenial and cingulate cortex	tissue	36.4
Temporal cortex	tissue	36.2
Hippocampal formation	tissue	36.1
Entorhinal cortex	tissue	36.1
Putamen	tissue	35.4
Olfactory bulb	tissue	34.9
Ventral forebrain	tissue	33.8
Cerebellum	tissue	33.5	medium
Amygdala	tissue	32.4
Periaqueductal gray	tissue	31.8
Parathyroid gland	tissue	31.2	medium
Basal ganglia	tissue	30.5	medium
Septum	tissue	29.4
Hypothalamus	tissue	28.9
Locus coeruleus	tissue	28.0
Salivary gland	tissue	24.9	medium
Vagina	tissue	24.6	high
Thymus	tissue	23.9
Kidney	tissue	22.5	medium
Pancreas	tissue	22.4	medium
Esophagus	tissue	22.2	high
Ovary	tissue	21.7	medium
Lung	tissue	21.5	high
Postcentral gyrus	tissue	21.1
Hippocampus	tissue	21.0	low
Smooth muscle	tissue	20.8	not detected
Colon	tissue	20.1	medium
Urinary bladder	tissue	20.1	high
Lymph node	tissue	19.2	not detected
Adipose tissue	tissue	19.2	high
Seminal vesicle	tissue	19.1	high
Adrenal gland	tissue	18.9	high
Liver	tissue	18.8	medium
Thyroid gland	tissue	18.4	medium
Fallopian tube	tissue	18.2	medium
Nucleus accumbens	tissue	18.1
Placenta	tissue	17.7	medium
Retina	tissue	17.4

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — White matter (49.9), Ventral spinal cord (46.5), Dorsal spinal cord (40.1), Blood vessel (34.8), Dorsal hippocampus (34.7).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting DMAC2 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 37 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-8080	99.82	67.52	1342
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-320A-3P	99.77	69.73	2107
HSA-MIR-320B	99.77	69.73	2107
HSA-MIR-320C	99.77	69.73	2107
HSA-MIR-320D	99.77	69.73	2107
HSA-MIR-4429	99.77	69.62	2111
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-561-3P	99.64	70.90	3647
HSA-MIR-3153	99.55	67.59	2337
HSA-MIR-671-5P	99.52	67.11	1277
HSA-MIR-3123	99.47	67.15	2693
HSA-MIR-4786-3P	99.36	68.35	1390
HSA-MIR-6128	99.33	67.83	1581
HSA-MIR-6828-5P	99.31	69.21	1433
HSA-MIR-4721	99.26	66.05	818
HSA-MIR-5589-5P	98.34	64.82	1148
HSA-MIR-653-3P	98.31	67.71	1542
HSA-MIR-4664-5P	98.17	65.07	1020
HSA-MIR-892B	98.00	67.11	821
HSA-MIR-6819-5P	97.96	66.59	1071
HSA-MIR-4446-3P	97.91	64.29	991
HSA-MIR-146B-3P	97.83	65.29	782
HSA-MIR-6737-5P	97.75	66.54	1044
HSA-MIR-634	97.74	67.11	818
HSA-MIR-6812-5P	97.56	65.39	1059
HSA-MIR-342-5P	97.25	64.10	817

Functional genomics

gnomAD constraint: pLI 9.74e-12, LOEUF 1.32, missense Z 0.669 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000221943 — one region, missense o/e 0.94.

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	dmac2	ENSDARG00000096597
mus_musculus	Dmac2	ENSMUSG00000057229
rattus_norvegicus	Dmac2	ENSRNOG00000020596
drosophila_melanogaster	CG4042	FBGN0037018
caenorhabditis_elegans		WBGENE00021815

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1913599) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 2 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal locomotor behavior	1
preweaning lethality, complete penetrance	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	Q4R5F9	85.2%	Diamond
Bos taurus	A6QNS9	74.4%	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
PCAT19	ncRNA	100505495
B3GNT8	protein-coding	374907
ERICH4	protein-coding	100170765
BCKDHA	protein-coding	593
EXOSC5	protein-coding	56915
TMEM91	protein-coding	641649
TGFB1	protein-coding	7040
B9D2	protein-coding	80776

Protein

Protein identifiers

Distal membrane-arm assembly complex protein 2 — Q9NW81 (reviewed: Q9NW81)

Alternative names: ATP synthase subunit s-like protein

All UniProt accessions (8): B4DFT4, Q9NW81, K7EIV4, K7ESN5, M0QX81, M0QZC4, M0QZP7, M0R078

UniProt curated annotations — full annotation on UniProt →

Function. Required for the assembly of the mitochondrial NADH:ubiquinone oxidoreductase complex (complex I). Involved in the assembly of the distal region of complex I.

Subunit / interactions. Interacts with incompletely assembled mitochondrial NADH:ubiquinone oxidoreductase complex (complex I).

Subcellular location. Mitochondrion.

Similarity. Belongs to the ATP synthase subunit s family.

Isoforms (6)

UniProt ID	Names	Canonical?
Q9NW81-1	1	yes
Q9NW81-2	2
Q9NW81-3	3
Q9NW81-4	4
Q9NW81-5	5
Q9NW81-6	6

RefSeq proteins (11): NP_001161339, NP_001161340, NP_001161341, NP_001161342, NP_001161343, NP_001307767, NP_001307768, NP_001307769, NP_001307770, NP_001307773, NP_060505* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR032675	LRR_dom_sf	Homologous_superfamily

UniProt features (11 total): sequence variant 5, splice variant 3, chain 1, modified residue 1, sequence conflict 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NW81-F1	79.56	0.63

Human Protein Atlas

Protein class: Predicted intracellular proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): mitochondria

Antibody reliability (HPA): IH approved · 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.

Post-translational modifications (1)

Type	Positions
Phosphoserine	253

Function

Pathways and Gene Ontology

Reactome pathways

1 curated (TAS) of 4; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

4 pathways:

ID	Pathway	Evidence
R-HSA-6799198	Complex I biogenesis	curated
R-HSA-1428517	Aerobic respiration and respiratory electron transport	—
R-HSA-1430728	Metabolism	—
R-HSA-611105	Respiratory electron transport	—

MSigDB gene sets: 107 (showing top): GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_MITOCHONDRIAL_RESPIRATORY_CHAIN_COMPLEX_ASSEMBLY, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, MCBRYAN_PUBERTAL_BREAST_4_5WK_DN, MCBRYAN_PUBERTAL_BREAST_5_6WK_UP, GOBP_SCF_DEPENDENT_PROTEASOMAL_UBIQUITIN_DEPENDENT_PROTEIN_CATABOLIC_PROCESS, NOUZOVA_TRETINOIN_AND_H4_ACETYLATION, GOBP_PROTEASOMAL_PROTEIN_CATABOLIC_PROCESS, IVANOVA_HEMATOPOIESIS_EARLY_PROGENITOR, GOBP_PROTEIN_CATABOLIC_PROCESS, SENESE_HDAC3_TARGETS_DN, GOCC_SCF_UBIQUITIN_LIGASE_COMPLEX, NUYTTEN_EZH2_TARGETS_DN

GO Biological Process (2): SCF-dependent proteasomal ubiquitin-dependent protein catabolic process (GO:0031146), mitochondrial respiratory chain complex I assembly (GO:0032981)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (2): mitochondrion (GO:0005739), SCF ubiquitin ligase complex (GO:0019005)

Reactome top-level categories

3 top-level categories:

Category	Pathways
Respiratory electron transport	1
Metabolism	1
Aerobic respiration and respiratory electron transport	1

GO top-level categories

7 GO namespaces:

Category	Terms
proteasome-mediated ubiquitin-dependent protein catabolic process	1
NADH dehydrogenase complex assembly	1
mitochondrial respiratory chain complex assembly	1
binding	1
cytoplasm	1
intracellular membrane-bounded organelle	1
cullin-RING ubiquitin ligase complex	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 2 of 5 annotations. The rest are phylogenetic / computational / electronic (IEA).

2 experimentally-supported GO terms:

GO term	NS	Evidence
mitochondrial respiratory chain complex I assembly	BP	mutant phenotype
mitochondrion	CC	high-throughput

Protein interactions and networks

STRING

showing 15 of 628 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DMAC2	TMEM186	Q96B77	667
DMAC2	TMEM70	Q9BUB7	646
DMAC2	FOXRED1	Q96CU9	639
DMAC2	TTC9B	Q8N6N2	593
DMAC2	DMAC1	Q96GE9	584
DMAC2	NDUFAF1	Q9Y375	518
DMAC2	IRGQ	Q8WZA9	494
DMAC2	TMEM126B	Q8IUX1	491
DMAC2	NDUFAF4	Q9P032	482
DMAC2	TIMMDC1	Q9NPL8	463
DMAC2	LRFN3	Q9BTN0	462
DMAC2	NDUFAF6	Q330K2	429
DMAC2	ACAD9	Q9H845	428
DMAC2	TULP2	O00295	417
DMAC2	ABRACL	Q9P1F3	413

Disease & clinical

Genetic variants

Variant evidence for DMAC2: 65 ClinVar records (0 pathogenic / likely pathogenic); 7 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	45
Likely benign	12
Benign	0

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 12 predictions of 497):

Position(s)	Effect	Δscore	Sites
19:41433674	acceptor_gain	1.0000
19:41433674–41433675	acceptor_loss	1.0000	3
19:41433682	acceptor_gain	1.0000
19:41436382	donor_gain	1.0000
19:41436404	donor_gain	1.0000
19:41432945	donor_gain	0.9900
19:41432969	donor_gain	0.9900
19:41433207	donor_gain	0.9900
19:41433259	donor_gain	0.9900
19:41433532	donor_loss	0.9900

AlphaMissense

322 missense substitutions predicted likely pathogenic (of 1,673 scored), across 106 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
N71	8	0.842	0.902
F100	7	0.941	0.985
W105	7	0.909	0.975
D163	7	0.891	0.937
C184	7	0.875	0.969
D162	7	0.870	0.936
F90	7	0.858	0.967
W164	7	0.830	0.920
C229	6	0.906	0.967
G191	6	0.844	0.957
G140	6	0.816	0.952
M225	6	0.807	0.839
C158	6	0.781	0.940
I187	5	0.817	0.924
K99	5	0.800	0.914
E224	5	0.757	0.842
V98	5	0.698	0.976
D205	5	0.683	0.749
L201	4	0.898	0.958
L179	4	0.892	0.971

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

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

3 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	8.64e-08
Kidney Renal Clear Cell Carcinoma (validation)	favorable	0.000224
Liver Hepatocellular Carcinoma (TCGA)	unfavorable	0.000302

Disease associations

OMIM: gene MIM:617262 | disease phenotypes:

GWAS associations

7 associations:

Study	Trait	p-value
GCST000817_58	Height	5e-16
GCST001714_2	Prostate cancer	2e-12
GCST012227_28	Hip circumference adjusted for BMI	6e-11
GCST008163_96	Height	4e-10
GCST90020028_1950	Hip circumference adjusted for BMI	4e-10
GCST001714_1	Prostate cancer	1e-8
GCST001119_2	Schizophrenia	1e-7

EFO canonical traits (from GWAS)

1 canonical traits:

EFO ID	Trait name
EFO:0008039	BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

11 total (human), top 11 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression	2
arsenite	affects binding, increases reaction	1
di-n-butylphosphoric acid	affects expression	1
Sunitinib	decreases expression	1
Acetaminophen	increases expression	1
Benzo(a)pyrene	increases methylation	1
Cadmium	decreases expression, increases abundance	1
Lead	affects splicing	1
Smoke	decreases expression	1
Tretinoin	decreases expression	1
Cadmium Chloride	decreases expression, increases abundance	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B1Q6	Abcam HeLa DMAC2 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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