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 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 65 total
• MANE Select transcript: NM_018035

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: 16 — 12 protein_coding, 3 retained_intron, 1 nonsense_mediated_decay

ENST00000221943, ENST00000301183, ENST00000417807, ENST00000438807, ENST00000586786, ENST00000589102, ENST00000589503, ENST00000589970, ENST00000590641, ENST00000592922, ENST00000594339, ENST00000594660, ENST00000595407, ENST00000595425, ENST00000597457, ENST00000597608

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.

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

292 total, 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

Single-cell (SCXA)

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

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

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

37 targeting DMAC2, 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-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

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

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): Q9NW81, B4DFT4, 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

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

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

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): 253

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-6799198	Complex I biogenesis

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

Rollup of top-1 pathways:

Category	Pathways
Respiratory electron transport	1

GO top-level categories

Rollup of top GO terms by namespace:

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

Protein interactions and networks

STRING

734 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DMAC2	FOXRED1	Q96CU9	835
DMAC2	TMEM70	Q9BUB7	796
DMAC2	DMAC1	Q96GE9	733
DMAC2	TMEM186	Q96B77	715
DMAC2	TTC9B	Q8N6N2	611
DMAC2	TIMMDC1	Q9NPL8	550
DMAC2	TMEM126B	Q8IUX1	520
DMAC2	IRGQ	Q8WZA9	520
DMAC2	NDUFAF1	Q9Y375	511
DMAC2	NDUFB11	Q9NX14	506
DMAC2	NDUFAF4	Q9P032	502
DMAC2	NDUFB10	O96000	501
DMAC2	NDUFB1	O75438	497
DMAC2	OXA1L	Q15070	493
DMAC2	NDUFB6	O95139	481

IntAct

10 interactions, top by confidence:

A	B	Type	Score
RCCD1	SPAG9	psi-mi:“MI:0914”(association)	0.640
SLC15A3		psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
MGARP	BTAF1	psi-mi:“MI:0914”(association)	0.350
AFG2A	ESYT2	psi-mi:“MI:0914”(association)	0.350
AFG2B	MMP24OS	psi-mi:“MI:0914”(association)	0.350
FECH	GTPBP10	psi-mi:“MI:0914”(association)	0.350
CELA3A	PIK3C2A	psi-mi:“MI:0914”(association)	0.350
SLC39A2	AGPAT2	psi-mi:“MI:0914”(association)	0.350

BioGRID (17): ATP5SL (Affinity Capture-RNA), ATP5SL (Affinity Capture-RNA), ATP5SL (Affinity Capture-RNA), ATP5SL (Affinity Capture-MS), ATP5SL (Affinity Capture-MS), ATP5SL (Affinity Capture-MS), ATP5SL (Affinity Capture-MS), ATP5SL (Affinity Capture-MS), ATP5SL (Positive Genetic), ATP5SL (Affinity Capture-RNA), ATP5SL (Affinity Capture-MS), ATP5SL (Affinity Capture-MS), ATP5SL (Affinity Capture-MS), ATP5SL (Affinity Capture-MS), ATP5SL (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A0A1B0GU71, A6QPI4, B2RV13, D4A6L0, E1BBQ2, F1LQY6, G3UW36, O08856, P15382, P53801, P55199, P56182, Q08CB3, Q0VF94, Q148E1, Q17RQ9, Q2KJ58, Q32Q90, Q4R5F9, Q4V8A6, Q4VA36, Q5I0I4, Q5NVI6, Q5R8Q2, Q5T6X4, Q5T848, Q5XII8, Q68EN5, Q6P767, Q8C419, Q8CHT6, Q8R143, Q8R1T1, Q8TBN0, Q8VDV3, Q8WUX9, Q90YH8, Q91WM6, Q91ZP9, Q96IL0

Diamond homologs: A6QNS9, Q4R5F9, Q5I0I4, Q9D7K5, Q9NW81, Q9VPC1, P22027, Q4R5S4, Q5R9E6, Q5XIM4, Q99766, Q9CRA7

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

959 predictions. Top by Δscore:

Variant	Effect	Δscore
19:41432944:AGCTT:A	donor_gain	1.0000
19:41432948:T:TA	donor_gain	1.0000
19:41433202:T:TA	donor_gain	1.0000
19:41433270:A:AC	donor_gain	1.0000
19:41433271:C:CC	donor_gain	1.0000
19:41433335:T:TA	donor_gain	1.0000
19:41433535:A:AC	donor_gain	1.0000
19:41433536:C:CT	donor_gain	1.0000
19:41433536:CGG:C	donor_gain	1.0000
19:41433536:CGGA:C	donor_gain	1.0000
19:41433536:CGGAG:C	donor_gain	1.0000
19:41433669:GAAAC:G	acceptor_gain	1.0000
19:41433670:AAAC:A	acceptor_gain	1.0000
19:41433671:AAC:A	acceptor_gain	1.0000
19:41433672:AC:A	acceptor_gain	1.0000
19:41433673:CC:C	acceptor_gain	1.0000
19:41433674:C:CC	acceptor_gain	1.0000
19:41433674:C:T	acceptor_gain	1.0000
19:41433674:CT:C	acceptor_loss	1.0000
19:41433681:C:CT	acceptor_gain	1.0000
19:41433682:G:T	acceptor_gain	1.0000
19:41436382:G:C	donor_gain	1.0000
19:41436390:A:AC	donor_gain	1.0000
19:41436391:C:CC	donor_gain	1.0000
19:41436391:CTTGA:C	donor_gain	1.0000
19:41436404:C:A	donor_gain	1.0000
19:41438415:C:CC	acceptor_gain	1.0000
19:41432945:G:C	donor_gain	0.9900
19:41432969:G:C	donor_gain	0.9900
19:41433207:T:A	donor_gain	0.9900

AlphaMissense

1673 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:41433670:A:C	F100L	0.985
19:41433670:A:T	F100L	0.985
19:41433672:A:G	F100L	0.985
19:41433588:C:G	A128P	0.980
19:41433341:A:G	L176S	0.976
19:41436395:A:T	V98D	0.976
19:41433657:A:G	W105R	0.975
19:41433657:A:T	W105R	0.975
19:41433671:A:G	F100S	0.972
19:41433332:A:T	L179H	0.971
19:41433318:A:G	C184R	0.969
19:41433655:C:A	W105C	0.969
19:41433655:C:G	W105C	0.969
19:41432318:G:C	C229W	0.967
19:41433332:A:G	L179P	0.967
19:41436418:G:C	F90L	0.967
19:41436418:G:T	F90L	0.967
19:41436420:A:G	F90L	0.967
19:41433410:A:G	L153S	0.966
19:41432319:C:T	C229Y	0.965
19:41433593:A:T	V126D	0.965
19:41432346:A:G	I220T	0.959
19:41432403:A:T	L201H	0.958
19:41433375:A:G	C165R	0.958
19:41433297:C:G	G191R	0.957
19:41433293:A:T	L192H	0.956
19:41433371:A:T	L166H	0.953
19:41433419:A:T	L150H	0.952
19:41433552:C:G	G140R	0.952
19:41433284:A:T	L195H	0.951

dbSNP variants (sampled 300 via entrez): RS1000173416 (19:41440070 G>A,C), RS1000399431 (19:41434106 G>A), RS1000673815 (19:41439809 C>T), RS1000798840 (19:41434478 A>G), RS1001221550 (19:41441427 C>G), RS1001390746 (19:41435469 C>T), RS1001569491 (19:41441599 G>T), RS1002961129 (19:41432326 G>A), RS1003286069 (19:41431486 C>T), RS1004511517 (19:41441114 C>G), RS1004555358 (19:41431438 G>A), RS1004641609 (19:41435120 C>T), RS1004766526 (19:41436566 C>G), RS1006867505 (19:41434785 A>G), RS1007204864 (19:41433512 C>A,G)

Disease associations

OMIM: gene MIM:617262 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST000817_179	Height	5.000000e-16
GCST001119_2	Schizophrenia	1.000000e-07
GCST001714_1	Prostate cancer	1.000000e-08
GCST001714_2	Prostate cancer	2.000000e-12
GCST008163_545	Height	4.000000e-10
GCST012227_1353	Hip circumference adjusted for BMI	6.000000e-11
GCST90020028_1331	Hip circumference adjusted for BMI	4.000000e-10

EFO canonical traits (1, from GWAS)

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

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

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	increases abundance, decreases expression	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)

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