DMAC1

Summary

DMAC1 (distal membrane arm assembly component 1, HGNC:30536) is a protein-coding gene on chromosome 9p24.1, encoding Distal membrane-arm assembly complex protein 1 (Q96GE9). Required for the assembly of the mitochondrial NADH:ubiquinone oxidoreductase complex (complex I).

Involved in mitochondrial respiratory chain complex I assembly. Located in mitochondrial inner membrane.

Source: NCBI Gene 90871 — RefSeq curated summary.

At a glance

• GWAS associations: 12
• Clinical variants (ClinVar): 31 total — 1 pathogenic
• MANE Select transcript: NM_033428

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30536
Approved symbol	DMAC1
Name	distal membrane arm assembly component 1
Location	9p24.1
Locus type	gene with protein product
Status	Approved
Aliases	MGC4730
Ensembl gene	ENSG00000137038
Ensembl biotype	protein_coding
OMIM	617261
Entrez	90871

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 3 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000358227, ENST00000469050, ENST00000484082, ENST00000880535, ENST00000929251

RefSeq mRNA: 3 — MANE Select: NM_033428 NM_001318058, NM_001318059, NM_033428

CCDS: CCDS34989

Canonical transcript exons

ENST00000358227 — 2 exons

Exon	Start	End
ENSE00000982130	7796500	7798637
ENSE00001164989	7799461	7799778

Expression profiles

Bgee: expression breadth ubiquitous, 255 present calls, max score 99.07.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 65.6826 / max 400.5872, expressed in 1820 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
99870	65.6826	1820

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left ventricle myocardium	UBERON:0006566	99.07	gold quality
cardiac muscle of right atrium	UBERON:0003379	98.83	gold quality
tibialis anterior	UBERON:0001385	98.73	gold quality
myocardium	UBERON:0002349	98.72	gold quality
ileal mucosa	UBERON:0000331	98.11	gold quality
heart right ventricle	UBERON:0002080	97.85	gold quality
quadriceps femoris	UBERON:0001377	97.77	gold quality
kidney epithelium	UBERON:0004819	97.72	gold quality
vastus lateralis	UBERON:0001379	97.55	gold quality
deltoid	UBERON:0001476	97.42	gold quality
apex of heart	UBERON:0002098	97.39	gold quality
biceps brachii	UBERON:0001507	97.08	gold quality
cardiac ventricle	UBERON:0002082	96.73	gold quality
heart left ventricle	UBERON:0002084	96.73	gold quality
skeletal muscle tissue	UBERON:0001134	96.65	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	96.54	gold quality
cardiac atrium	UBERON:0002081	96.47	gold quality
right atrium auricular region	UBERON:0006631	96.37	gold quality
pancreatic ductal cell	CL:0002079	96.31	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	96.31	gold quality
heart	UBERON:0000948	96.26	gold quality
stromal cell of endometrium	CL:0002255	96.25	gold quality
mucosa of transverse colon	UBERON:0004991	96.19	gold quality
muscle tissue	UBERON:0002385	96.11	gold quality
hindlimb stylopod muscle	UBERON:0004252	96.09	gold quality
gastrocnemius	UBERON:0001388	96.04	gold quality
muscle of leg	UBERON:0001383	95.86	gold quality
thymus	UBERON:0002370	95.60	gold quality
body of tongue	UBERON:0011876	95.59	gold quality
mucosa of sigmoid colon	UBERON:0004993	95.06	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-125970	yes	41.93
E-ANND-3	yes	8.83
E-MTAB-7303	no	530.82

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

89 targeting DMAC1, 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-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-3617-3P	99.98	67.86	918
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-3682-5P	99.93	67.97	1163
HSA-MIR-552-5P	99.93	68.56	1583
HSA-MIR-380-3P	99.89	70.18	1978
HSA-MIR-369-3P	99.85	70.52	2264
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-548A-3P	99.76	70.58	3524
HSA-MIR-3617-5P	99.75	69.41	1968
HSA-MIR-641	99.75	69.35	1975
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-4524A-3P	99.72	66.85	2406
HSA-MIR-3975	99.62	65.97	697

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Dmac1	ENSMUSG00000028398
rattus_norvegicus	Dmac1	ENSRNOG00000023946

Protein

Protein identifiers

Distal membrane-arm assembly complex protein 1 — Q96GE9 (reviewed: Q96GE9)

Alternative names: Transmembrane protein 261

All UniProt accessions (1): Q96GE9

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 inner membrane.

Isoforms (2)

UniProt ID	Names	Canonical?
Q96GE9-1	1	yes
Q96GE9-2	2

RefSeq proteins (3): NP_001304987, NP_001304988, NP_219500* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR028036	DMAC1-like_dom	Domain
IPR053117	DMAC_Protein	Family

Pfam: PF15055

UniProt features (7 total): transmembrane region 2, chain 1, region of interest 1, compositionally biased region 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96GE9-F1	60.00	0.00

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-6799198	Complex I biogenesis

MSigDB gene sets: 119 (showing top): STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_MITOCHONDRIAL_RESPIRATORY_CHAIN_COMPLEX_ASSEMBLY, CHARAFE_BREAST_CANCER_BASAL_VS_MESENCHYMAL_UP, GOCC_MITOCHONDRIAL_ENVELOPE, OSMAN_BLADDER_CANCER_DN, GOCC_ORGANELLE_INNER_MEMBRANE, MARSON_BOUND_BY_FOXP3_STIMULATED, MARSON_BOUND_BY_FOXP3_UNSTIMULATED, GOCC_ORGANELLE_ENVELOPE, MARTENS_TRETINOIN_RESPONSE_DN, GOBP_NADH_DEHYDROGENASE_COMPLEX_ASSEMBLY, REACTOME_COMPLEX_I_BIOGENESIS, GOBP_MITOCHONDRION_ORGANIZATION

GO Biological Process (1): mitochondrial respiratory chain complex I assembly (GO:0032981)

GO Molecular Function (0):

GO Cellular Component (3): mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), membrane (GO:0016020)

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
NADH dehydrogenase complex assembly	1
mitochondrial respiratory chain complex assembly	1
cytoplasm	1
intracellular membrane-bounded organelle	1
organelle inner membrane	1
mitochondrial membrane	1
cellular anatomical structure	1

Protein interactions and networks

STRING

562 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DMAC1	DMAC2	Q9NW81	733
DMAC1	FOXRED1	Q96CU9	610
DMAC1	RIC1	Q4ADV7	527
DMAC1	SPATA6L	Q8N4H0	476
DMAC1	TMEM186	Q96B77	457
DMAC1	OXA1L	Q15070	448
DMAC1	ARMC7	Q9H6L4	444
DMAC1	KLHDC4	Q8TBB5	432
DMAC1	ZNF185	O15231	421
DMAC1	UHRF2	Q96PU4	404
DMAC1	TIMMDC1	Q9NPL8	402
DMAC1	TMEM41B	Q5BJD5	392
DMAC1	C15orf61	A6NNL5	391
DMAC1	TMEM126B	Q8IUX1	389
DMAC1	SYTL3	Q4VX76	377

IntAct

7 interactions, top by confidence:

A	B	Type	Score
MGARP	RTL8C	psi-mi:“MI:0914”(association)	0.350
SLC25A1	CYC1	psi-mi:“MI:0914”(association)	0.350
MFSD5	ILVBL	psi-mi:“MI:0914”(association)	0.350
SLC35F2	EI24	psi-mi:“MI:0914”(association)	0.350
SLC6A3	GET1	psi-mi:“MI:0914”(association)	0.350
DMAC1	uup	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (27): TMEM261 (Affinity Capture-MS), TMEM261 (Positive Genetic), TMEM261 (Negative Genetic), TMEM261 (Positive Genetic), TMEM261 (Negative Genetic), TMEM261 (Negative Genetic), TMEM261 (Positive Genetic), TMEM261 (Negative Genetic), TMEM261 (Negative Genetic), TMEM261 (Negative Genetic), TMEM261 (Negative Genetic), TMEM261 (Positive Genetic), TMEM261 (Positive Genetic), TOMM22 (Negative Genetic), UQCRB (Positive Genetic)

ESM2 similar proteins: A0A096LP01, A2AJB2, A3LP48, A5DJS9, A5E5Y6, A7TQD5, B2RZD2, B9WD58, C4XZH2, C4YPM0, C5DE77, C5DQU6, C5M8B9, G2TRP9, O22912, O95167, P0DN34, P0DN35, P19173, Q02371, Q04935, Q0D285, Q0MQ95, Q12082, Q2KP58, Q3E776, Q3E823, Q3SZU9, Q42841, Q56VL3, Q59LP6, Q6BYM1, Q6C0R5, Q6CMH6, Q75D07, Q86IZ2, Q8IUX1, Q8VY39, Q8VY40, Q941A6

Diamond homologs: Q96GE9, Q9CQ00

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	26
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1711163	GRCh37/hg19 9p24.1-23(chr9:6825346-10816593)x1	Pathogenic

SpliceAI

537 predictions. Top by Δscore:

Variant	Effect	Δscore
9:7799459:A:AC	donor_gain	0.9900
9:7799460:C:CC	donor_gain	0.9900
9:7799429:AAC:A	donor_gain	0.9600
9:7798638:C:CC	acceptor_gain	0.9200
9:7798526:C:CT	acceptor_gain	0.9100
9:7799408:T:TA	donor_gain	0.9100
9:7799428:CA:C	donor_gain	0.9100
9:7799429:AA:A	donor_gain	0.9100
9:7799463:AGG:A	donor_gain	0.9100
9:7799577:A:C	donor_gain	0.9100
9:7799602:TCA:T	donor_gain	0.9000
9:7798634:ATGCC:A	acceptor_loss	0.8900
9:7798635:TGCCT:T	acceptor_loss	0.8900
9:7798638:CT:C	acceptor_loss	0.8900
9:7798639:T:G	acceptor_loss	0.8900
9:7799447:G:A	donor_gain	0.8900
9:7799590:T:TA	donor_gain	0.8900
9:7799584:G:GT	donor_gain	0.8800
9:7798316:T:A	donor_gain	0.8700
9:7798635:TGC:T	acceptor_gain	0.8700
9:7799751:TCA:T	donor_gain	0.8700
9:7798968:CA:C	donor_gain	0.8600
9:7799425:AC:A	donor_gain	0.8600
9:7799426:CC:C	donor_gain	0.8600
9:7799427:CC:C	donor_gain	0.8600
9:7799568:A:AT	donor_gain	0.8600
9:7799602:T:TA	donor_gain	0.8600
9:7799721:A:AT	donor_gain	0.8600
9:7798528:C:CT	acceptor_gain	0.8400
9:7799752:CA:C	donor_gain	0.8400

AlphaMissense

708 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1001325260 (9:7801051 A>C,G), RS1001818165 (9:7801310 C>A,G,T), RS1002761355 (9:7797953 A>C,G), RS1002878047 (9:7796136 C>G,T), RS1003251246 (9:7800871 C>T), RS1003832153 (9:7796768 A>T), RS1004163259 (9:7796899 C>G,T), RS1004227252 (9:7800114 A>G), RS1005103847 (9:7800756 T>A), RS1005157756 (9:7800491 A>C,G), RS1005224103 (9:7799212 C>A), RS1005234595 (9:7799600 C>T), RS1006270661 (9:7798327 A>G), RS1006567620 (9:7801559 T>G), RS1007242724 (9:7800475 G>A,T)

Disease associations

OMIM: gene MIM:617261 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

12 associations (top):

Study	Trait	p-value
GCST003434_8	Obsessive-compulsive symptoms	6.000000e-06
GCST003479_3	Hair color	2.000000e-06
GCST007096_136	Pulse pressure	6.000000e-09
GCST007099_141	Systolic blood pressure	7.000000e-09
GCST007159_5	Corneal astigmatism	5.000000e-06
GCST009391_2080	Metabolite levels	8.000000e-06
GCST011703_92	Smoking initiation	3.000000e-08
GCST011743_20	HDL cholesterol levels in HIV infection	8.000000e-06
GCST012020_575	Serum metabolite levels	1.000000e-10
GCST012021_23	Serum metabolite levels	1.000000e-10
GCST012145_12	Ferritin levels	8.000000e-07
GCST012145_24	Ferritin levels	1.000000e-07

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0007802	obsessive-compulsive symptom measurement
EFO:0005763	pulse pressure measurement
EFO:0006335	systolic blood pressure
EFO:1002040	Corneal astigmatism
EFO:0010372	phosphatidylcholine 32:0 measurement
EFO:0005670	smoking initiation
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004459	ferritin measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects expression, decreases expression, increases expression	3
methylparaben	decreases expression	2
Valproic Acid	affects expression, increases expression	2
methylmercuric chloride	decreases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
arsenite	affects binding, increases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cobaltous chloride	decreases expression	1
butyraldehyde	decreases expression	1
pentanal	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
K 7174	decreases expression	1
jinfukang	increases expression	1
Venlafaxine Hydrochloride	increases expression	1
Resveratrol	decreases expression, increases expression, affects cotreatment	1
Sunitinib	decreases expression	1
Cadmium	increases abundance, increases expression	1
Carbamazepine	affects expression	1
Doxorubicin	increases expression	1
Ethyl Methanesulfonate	decreases expression	1
Methyl Methanesulfonate	decreases expression	1
Phthalic Acids	increases methylation	1
Plant Extracts	increases expression, affects cotreatment, decreases expression	1
Thiram	decreases expression	1
Tretinoin	decreases expression	1
Urethane	decreases expression	1
Cyclosporine	decreases expression	1
Cadmium Chloride	increases abundance, increases expression	1
Lactic Acid	decreases expression	1

Clinical trials (associated diseases)

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