DRC8

Summary

DRC8 (dynein regulatory complex subunit 8, HGNC:28166) is a protein-coding gene on chromosome 1q44, encoding Dynein regulatory complex protein 8 (Q5VUJ9). Component of the nexin-dynein regulatory complex (N-DRC), a key regulator of ciliary/flagellar motility which maintains the alignment and integrity of the distal axoneme and regulates microtubule sliding in motile axonemes.

The gene encodes a protein that contains two EF-hand calcium-binding domains although its function has yet to be determined. Alternatively spliced transcripts have been observed.

Source: NCBI Gene 84288 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 45 total — 1 pathogenic
• MANE Select transcript: NM_032328

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28166
Approved symbol	DRC8
Name	dynein regulatory complex subunit 8
Location	1q44
Locus type	gene with protein product
Status	Approved
Aliases	MGC12458, DRC8, CFAP200
Ensembl gene	ENSG00000203666
Ensembl biotype	protein_coding
OMIM	619617
Entrez	84288

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 10 protein_coding_CDS_not_defined, 9 protein_coding, 1 retained_intron

ENST00000366521, ENST00000366522, ENST00000366523, ENST00000391837, ENST00000425550, ENST00000427529, ENST00000447569, ENST00000473686, ENST00000479260, ENST00000479923, ENST00000487845, ENST00000495271, ENST00000497591, ENST00000518607, ENST00000549220, ENST00000551317, ENST00000923177, ENST00000923178, ENST00000948552, ENST00000948553

RefSeq mRNA: 3 — MANE Select: NM_032328 NM_001143943, NM_001290327, NM_032328

CCDS: CCDS31082, CCDS44341

Canonical transcript exons

ENST00000366523 — 8 exons

Exon	Start	End
ENSE00001441912	245087245	245087837
ENSE00001441918	244970329	244970443
ENSE00001441919	244969682	244970043
ENSE00003474675	245082083	245082162
ENSE00003508345	245017242	245017326
ENSE00003581081	245083622	245083688
ENSE00003620816	245083442	245083484
ENSE00003640672	245059386	245059458

Expression profiles

Bgee: expression breadth ubiquitous, 265 present calls, max score 98.35.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 18.7083 / max 362.1768, expressed in 1802 samples.

FANTOM5 promoters (13 alternative TSS)

Promoter ID	TPM avg	Samples expressed
9508	7.7419	1626
9500	2.3998	460
9502	1.5914	393
9506	1.4686	727
9505	1.2409	588
9501	1.1634	235
9509	0.9607	377
9507	0.7744	425
9504	0.4915	234
202032	0.4257	204

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	98.35	gold quality
calcaneal tendon	UBERON:0003701	94.30	gold quality
sural nerve	UBERON:0015488	94.08	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	93.23	gold quality
bronchial epithelial cell	CL:0002328	93.10	gold quality
left lobe of thyroid gland	UBERON:0001120	92.06	gold quality
right testis	UBERON:0004534	91.96	gold quality
right lobe of thyroid gland	UBERON:0001119	91.95	gold quality
left testis	UBERON:0004533	91.81	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	91.62	gold quality
thyroid gland	UBERON:0002046	91.44	gold quality
mucosa of stomach	UBERON:0001199	91.28	gold quality
epithelium of bronchus	UBERON:0002031	91.05	gold quality
right atrium auricular region	UBERON:0006631	91.05	gold quality
tibial nerve	UBERON:0001323	90.95	gold quality
endocervix	UBERON:0000458	90.94	gold quality
heart left ventricle	UBERON:0002084	90.84	gold quality
cardiac ventricle	UBERON:0002082	90.53	gold quality
spinal cord	UBERON:0002240	90.52	gold quality
left uterine tube	UBERON:0001303	90.51	gold quality
hindlimb stylopod muscle	UBERON:0004252	90.48	gold quality
bronchus	UBERON:0002185	90.39	gold quality
muscle of leg	UBERON:0001383	90.03	gold quality
gastrocnemius	UBERON:0001388	90.02	gold quality
testis	UBERON:0000473	89.87	gold quality
body of pancreas	UBERON:0001150	89.83	gold quality
right adrenal gland cortex	UBERON:0035827	89.79	gold quality
heart	UBERON:0000948	89.61	gold quality
right adrenal gland	UBERON:0001233	89.31	gold quality
left adrenal gland	UBERON:0001234	89.25	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-7303	no	296.24
E-GEOD-124858	no	81.71
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

110 targeting DRC8, 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-432-3P	100.00	67.86	705
HSA-MIR-6740-5P	100.00	65.64	932
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-8075	99.97	67.20	962
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-6744-5P	99.93	66.82	748
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-4766-5P	99.75	69.23	2662
HSA-MIR-7856-5P	99.75	69.99	2901
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-10393-3P	99.72	66.56	961
HSA-MIR-6801-5P	99.72	66.50	981
HSA-MIR-1296-3P	99.72	64.04	636
HSA-MIR-30B-3P	99.70	65.76	2325
HSA-MIR-3689A-3P	99.70	65.73	2306

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
mus_musculus	Efcab2	ENSMUSG00000026495
rattus_norvegicus	Efcab2	ENSRNOG00000042201
drosophila_melanogaster	CG9406	FBGN0034592
caenorhabditis_elegans		WBGENE00000285
caenorhabditis_elegans		WBGENE00000287
caenorhabditis_elegans	pat-10	WBGENE00003934
caenorhabditis_elegans		WBGENE00008453
caenorhabditis_elegans	F35C12.3	WBGENE00009408
caenorhabditis_elegans		WBGENE00015264

Paralogs (20): CABP7 (ENSG00000100314), CABP5 (ENSG00000105507), CALML4 (ENSG00000129007), CALM2 (ENSG00000143933), CETN2 (ENSG00000147400), CETN3 (ENSG00000153140), CABP1 (ENSG00000157782), CALM3 (ENSG00000160014), CABP2 (ENSG00000167791), CALML6 (ENSG00000169885), EFCAB3 (ENSG00000172421), EFCAB12 (ENSG00000172771), CABP4 (ENSG00000175544), CETN1 (ENSG00000177143), CALML3 (ENSG00000178363), CALML5 (ENSG00000178372), CALN1 (ENSG00000183166), CALM1 (ENSG00000198668), EFCAB7 (ENSG00000203965), EFCAB9 (ENSG00000214360)

Protein

Protein identifiers

Dynein regulatory complex protein 8 — Q5VUJ9 (reviewed: Q5VUJ9)

Alternative names: EF-hand calcium-binding domain-containing protein 2

All UniProt accessions (4): Q5VUJ9, H0Y588, H0Y6F0, H0YHT5

UniProt curated annotations — full annotation on UniProt →

Function. Component of the nexin-dynein regulatory complex (N-DRC), a key regulator of ciliary/flagellar motility which maintains the alignment and integrity of the distal axoneme and regulates microtubule sliding in motile axonemes.

Subunit / interactions. Component of the nexin-dynein regulatory complex (N-DRC).

Subcellular location. Cytoplasm. Cytoskeleton. Flagellum axoneme.

Similarity. Belongs to the DRC8 family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q5VUJ9-1	1	yes
Q5VUJ9-2	2
Q5VUJ9-3	3

RefSeq proteins (3): NP_001137415, NP_001277256, NP_115704* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002048	EF_hand_dom	Domain
IPR011992	EF-hand-dom_pair	Homologous_superfamily

UniProt features (11 total): splice variant 5, domain 2, chain 1, sequence conflict 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
8J07	ELECTRON MICROSCOPY	4.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5VUJ9-F1	65.45	0.11

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 123 (showing top): GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN, YY1_02, GOBP_CILIUM_MOVEMENT, GOBP_CILIUM_OR_FLAGELLUM_DEPENDENT_CELL_MOTILITY, LIAO_METASTASIS, MODULE_397, chr1q44, SENESE_HDAC3_TARGETS_DN, GOCC_CYTOPLASMIC_REGION, GOCC_MOTILE_CILIUM, MARSON_BOUND_BY_FOXP3_STIMULATED, MARSON_BOUND_BY_FOXP3_UNSTIMULATED, GOCC_SPERM_PRINCIPAL_PIECE, GOCC_CILIUM

GO Biological Process (0):

GO Molecular Function (2): calcium ion binding (GO:0005509), protein binding (GO:0005515)

GO Cellular Component (7): sperm principal piece (GO:0097228), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), cilium (GO:0005929), motile cilium (GO:0031514), cell projection (GO:0042995), organelle (GO:0043226)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
metal ion binding	1
binding	1
sperm flagellum	1
intracellular anatomical structure	1
intracellular membraneless organelle	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1
cilium	1

Protein interactions and networks

STRING

1611 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DRC8	DRC5	Q5JU00	591
DRC8	DRC10	Q96DY2	591
DRC8	DRC7	Q8IY82	583
DRC8	DRC11	Q86XH1	578
DRC8	HRC	P23327	517
DRC8	COX20	Q5RI15	508
DRC8	GIN1	Q9NXP7	507
DRC8	PPEF2	O14830	501
DRC8	EFCAB11	Q9BUY7	497
DRC8	TTLL7	Q6ZT98	457
DRC8	DRC4	O95995	451
DRC8	KIF26B	Q2KJY2	448
DRC8	PPP1R21	Q6ZMI0	446
DRC8	KLHL30	Q0D2K2	442
DRC8	DRC9	Q9H095	434

IntAct

5 interactions, top by confidence:

A	B	Type	Score
TEX36	EFCAB2	psi-mi:“MI:0915”(physical association)	0.400
C2orf66	EFCAB2	psi-mi:“MI:0915”(physical association)	0.400
IQCN	TARS3	psi-mi:“MI:0914”(association)	0.350
EFCAB2	IQGAP2	psi-mi:“MI:0914”(association)	0.350

BioGRID (16): EFCAB2 (Affinity Capture-MS), EFCAB2 (Affinity Capture-MS), EFCAB2 (Two-hybrid), EFCAB2 (Two-hybrid), EFCAB2 (Two-hybrid), TCL1B (Two-hybrid), MRPL12 (Two-hybrid), EFCAB2 (Affinity Capture-MS), IQGAP2 (Affinity Capture-MS), EFCAB2 (Affinity Capture-MS), UBE3B (Affinity Capture-MS), EFCAB2 (Affinity Capture-MS), MTHFSD (Affinity Capture-MS), CEP131 (Affinity Capture-MS), EFCAB2 (Affinity Capture-RNA)

ESM2 similar proteins: A0A8I5KY20, A4IHR5, A7UKY7, A8IHN8, D3YYI7, G3V9M2, O43559, P39881, P49796, Q13387, Q14DQ1, Q2TAM9, Q32KV8, Q3UPL5, Q4VA45, Q5VUJ9, Q5VV17, Q5XKK7, Q62392, Q673H1, Q6NV74, Q6PJ61, Q6QHK4, Q6UXB0, Q7Z6J2, Q80TE3, Q86SH2, Q8BWU3, Q8CE64, Q8IWP9, Q8N554, Q8NFT6, Q8R4T5, Q8TC41, Q8VCC6, Q8WV24, Q96HA4, Q96IQ9, Q96SQ7, Q96T92

Diamond homologs: A3E3H0, A3E4D8, A3E4F9, A4UHC0, A8CEP3, A8I1Q0, O00897, O02367, O16305, O60041, O82018, O94739, O96081, O97341, P02585, P02586, P02587, P02588, P02589, P02597, P02598, P02599, P04352, P04464, P05419, P05932, P05933, P06787, P07463, P0DP23, P0DP24, P0DP25, P0DP26, P0DP27, P0DP28, P0DP29, P0DP30, P0DP31, P0DP33, P0DP34

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
EFCAB2	“form complex”	“Nexin-dynein regulatory complex”	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	20
Likely benign	3
Benign	2

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1180520	GRCh37/hg19 1q44(chr1:244811325-245725982)x1	Pathogenic

SpliceAI

2118 predictions. Top by Δscore:

Variant	Effect	Δscore
1:245014254:GGT:G	donor_gain	1.0000
1:245014256:T:G	donor_gain	1.0000
1:245017239:CAG:C	acceptor_gain	1.0000
1:245017240:A:AG	acceptor_gain	1.0000
1:245017240:AGA:A	acceptor_gain	1.0000
1:245017241:G:GG	acceptor_gain	1.0000
1:245017241:GA:G	acceptor_gain	1.0000
1:245017241:GAG:G	acceptor_gain	1.0000
1:245082079:TTAGG:T	acceptor_loss	1.0000
1:245082080:TA:T	acceptor_loss	1.0000
1:245082081:A:AC	acceptor_loss	1.0000
1:245082082:GGTA:G	acceptor_gain	1.0000
1:245082158:AGAAA:A	donor_gain	1.0000
1:245082159:GAAA:G	donor_gain	1.0000
1:245082159:GAAAG:G	donor_gain	1.0000
1:245082161:AA:A	donor_gain	1.0000
1:245082162:AGTA:A	donor_loss	1.0000
1:245082163:G:C	donor_loss	1.0000
1:245082163:G:GG	donor_gain	1.0000
1:245082164:T:G	donor_loss	1.0000
1:245082164:TAA:T	donor_gain	1.0000
1:245082167:G:GG	donor_gain	1.0000
1:245083620:A:AG	acceptor_gain	1.0000
1:245083620:AG:A	acceptor_gain	1.0000
1:245083621:G:A	acceptor_gain	1.0000
1:245083621:G:GT	acceptor_gain	1.0000
1:245083621:GGT:G	acceptor_gain	1.0000
1:245083621:GGTT:G	acceptor_gain	1.0000
1:245083621:GGTTT:G	acceptor_gain	1.0000
1:245083684:AGAAG:A	donor_gain	1.0000

AlphaMissense

1074 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:245017283:T:C	F159L	0.999
1:245017285:T:A	F159L	0.999
1:245017285:T:G	F159L	0.999
1:245017292:T:C	F162L	0.999
1:245017294:T:A	F162L	0.999
1:245017294:T:G	F162L	0.999
1:245059439:T:C	L191P	0.999
1:245059448:T:C	L194P	0.999
1:245082126:T:C	F212S	0.999
1:245017284:T:C	F159S	0.998
1:245017317:T:A	V170E	0.998
1:245059400:T:A	I178N	0.998
1:245059406:G:T	R180M	0.998
1:245059408:T:C	S181P	0.998
1:245082125:T:C	F212L	0.998
1:245082127:T:A	F212L	0.998
1:245082127:T:G	F212L	0.998
1:245083479:T:C	F237L	0.998
1:245083481:T:A	F237L	0.998
1:245083481:T:G	F237L	0.998
1:245083665:T:C	L253P	0.998
1:245017284:T:G	F159C	0.997
1:245017320:A:T	D171V	0.997
1:245059394:G:A	G176E	0.997
1:245059400:T:G	I178S	0.997
1:245059406:G:C	R180T	0.997
1:245059407:G:C	R180S	0.997
1:245059407:G:T	R180S	0.997
1:245082111:T:A	I207N	0.997
1:245083480:T:C	F237S	0.997

dbSNP variants (sampled 300 via entrez): RS1000020079 (1:245006807 G>A,C), RS1000041556 (1:244992515 G>A), RS1000055349 (1:245077846 G>T), RS1000080039 (1:245011180 G>A,C), RS1000090824 (1:244999951 T>A,C), RS1000130972 (1:244981597 G>A,T), RS1000145595 (1:245073597 T>C), RS1000161522 (1:245096303 G>C), RS1000203100 (1:245066831 C>T), RS1000215686 (1:245042073 C>A), RS1000224954 (1:245024273 T>C), RS1000251960 (1:245029586 A>C,G), RS1000296566 (1:245113823 C>A,T), RS1000311379 (1:245119825 C>T), RS1000319958 (1:245119685 A>G)

Disease associations

OMIM: gene MIM:619617 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST003263_109	Post bronchodilator FEV1 in COPD	2.000000e-06
GCST003518_26	Daytime sleep phenotypes	3.000000e-06
GCST003518_40	Daytime sleep phenotypes	8.000000e-06
GCST007552_32	Colorectal cancer	5.000000e-08
GCST009391_50	Metabolite levels	5.000000e-06
GCST011743_69	HDL cholesterol levels in HIV infection	5.000000e-06

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004314	forced expiratory volume
EFO:0007828	daytime rest measurement
EFO:0009777	citrulline measurement
EFO:0004612	high density lipoprotein cholesterol measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression	4
sodium arsenite	decreases expression, increases abundance, increases expression	3
Arsenic	affects expression, affects methylation, increases abundance, increases expression	3
Benzo(a)pyrene	decreases expression, affects methylation	3
Cyclosporine	increases expression	3
perfluorooctane sulfonic acid	increases expression	2
Tretinoin	decreases expression, increases expression	2
aristolochic acid I	decreases expression	1
urushiol	increases expression	1
propionaldehyde	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
butyraldehyde	decreases expression	1
pentanal	decreases expression	1
perfluoro-n-nonanoic acid	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
perfluorohexanesulfonic acid	increases expression	1
belinostat	decreases expression	1
dorsomorphin	decreases expression, affects cotreatment	1
NSC 689534	increases expression, affects binding	1
MT19c compound	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Sunitinib	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Aldehydes	decreases expression	1
Cadmium	decreases expression, increases abundance	1
Copper	affects binding, increases expression	1
Doxorubicin	decreases expression	1
Methyl Methanesulfonate	increases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Smoke	increases abundance, increases expression	1

Clinical trials (associated diseases)

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