DRC5

Summary

DRC5 (dynein regulatory complex subunit 5, HGNC:11693) is a protein-coding gene on chromosome 6p21.1, encoding Dynein regulatory complex subunit 5 (Q5JU00). 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.

Predicted to be involved in flagellated sperm motility. Predicted to be located in sperm flagellum.

Source: NCBI Gene 202500 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 51 total
• MANE Select transcript: NM_182539

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11693
Approved symbol	DRC5
Name	dynein regulatory complex subunit 5
Location	6p21.1
Locus type	gene with protein product
Status	Approved
Aliases	D6S46, MGC33600, FAP155
Ensembl gene	ENSG00000146221
Ensembl biotype	protein_coding
OMIM	186975
Entrez	202500

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000371504, ENST00000371505, ENST00000897136

RefSeq mRNA: 1 — MANE Select: NM_182539 NM_182539

CCDS: CCDS4910

Canonical transcript exons

ENST00000371505 — 5 exons

Exon	Start	End
ENSE00001140259	44282110	44282559
ENSE00001888440	44297659	44297698
ENSE00001909679	44278734	44280390
ENSE00003465359	44287549	44287918
ENSE00003680700	44285964	44286532

Expression profiles

Bgee: expression breadth ubiquitous, 127 present calls, max score 89.63.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.2412 / max 97.8854, expressed in 85 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
73769	0.1278	52
73770	0.0617	32
73767	0.0297	3
73768	0.0141	5
73766	0.0079	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	89.63	gold quality
left testis	UBERON:0004533	87.25	gold quality
right testis	UBERON:0004534	87.19	gold quality
sperm	CL:0000019	84.40	silver quality
testis	UBERON:0000473	84.00	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	81.16	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	77.80	gold quality
cerebellar hemisphere	UBERON:0002245	73.73	gold quality
cerebellar cortex	UBERON:0002129	73.64	gold quality
right hemisphere of cerebellum	UBERON:0014890	73.07	gold quality
cerebellum	UBERON:0002037	71.57	gold quality
prefrontal cortex	UBERON:0000451	67.27	gold quality
cortical plate	UBERON:0005343	65.75	gold quality
bronchial epithelial cell	CL:0002328	65.15	silver quality
bronchus	UBERON:0002185	64.03	silver quality
right frontal lobe	UBERON:0002810	63.26	gold quality
Brodmann (1909) area 9	UBERON:0013540	61.88	gold quality
nasal cavity mucosa	UBERON:0001826	61.72	gold quality
anterior cingulate cortex	UBERON:0009835	61.27	gold quality
frontal cortex	UBERON:0001870	61.26	gold quality
hypothalamus	UBERON:0001898	61.06	gold quality
neocortex	UBERON:0001950	60.92	gold quality
ganglionic eminence	UBERON:0004023	60.79	gold quality
nucleus accumbens	UBERON:0001882	60.69	gold quality
fallopian tube	UBERON:0003889	60.47	gold quality
amygdala	UBERON:0001876	60.42	gold quality
caudate nucleus	UBERON:0001873	59.87	gold quality
adult organism	UBERON:0007023	59.86	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	59.30	gold quality
right lung	UBERON:0002167	59.06	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.85

Regulation

Is transcription factor: no

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	tcte1	ENSDARG00000077387
mus_musculus	Tcte1	ENSMUSG00000023949
rattus_norvegicus	Tcte1	ENSRNOG00000065569
drosophila_melanogaster	CG14325	FBGN0038531

Protein

Protein identifiers

Dynein regulatory complex subunit 5 — Q5JU00 (reviewed: Q5JU00)

Alternative names: T-complex-associated testis-expressed protein 1

All UniProt accessions (2): Q5JU00, Q5JU01

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. May play a role in the assembly of N-DRC. May be required for sperm motility.

Subunit / interactions. Component of the nexin-dynein regulatory complex (N-DRC). Interacts with DRC1. Interacts with FBXL13/DRC6, DRC3 and DRC7.

Subcellular location. Cell projection. Cilium. Flagellum. Cytoplasm. Cytoskeleton. Flagellum axoneme.

Similarity. Belongs to the DRC5 family.

RefSeq proteins (1): NP_872345* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001611	Leu-rich_rpt	Repeat
IPR032675	LRR_dom_sf	Homologous_superfamily
IPR052410	DRC5	Family

Pfam: PF13516

UniProt features (13 total): repeat 5, sequence variant 3, region of interest 2, compositionally biased region 2, chain 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-Q5JU00-F1	83.02	0.70

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 55 (showing top): BENPORATH_ES_WITH_H3K27ME3, DARWICHE_SKIN_TUMOR_PROMOTER_DN, DARWICHE_PAPILLOMA_RISK_LOW_UP, DARWICHE_PAPILLOMA_RISK_HIGH_DN, DARWICHE_SQUAMOUS_CELL_CARCINOMA_DN, GOBP_CILIUM_MOVEMENT, GOBP_CILIUM_OR_FLAGELLUM_DEPENDENT_CELL_MOTILITY, GOCC_CYTOPLASMIC_REGION, GOCC_MOTILE_CILIUM, GOCC_CILIUM, MIKKELSEN_MCV6_HCP_WITH_H3K27ME3, MIKKELSEN_MEF_HCP_WITH_H3K27ME3, GOCC_9PLUS2_MOTILE_CILIUM, ZWANG_TRANSIENTLY_UP_BY_2ND_EGF_PULSE_ONLY, FOXN3_TARGET_GENES

GO Biological Process (2): microtubule-based movement (GO:0007018), flagellated sperm motility (GO:0030317)

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

GO Cellular Component (6): sperm flagellum (GO:0036126), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), cilium (GO:0005929), motile cilium (GO:0031514), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
microtubule-based process	1
cilium-dependent cell motility	1
cilium movement involved in cell motility	1
sperm motility	1
binding	1
9+2 motile cilium	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

1006 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DRC5	DYNLT2	Q8IZS6	830
DRC5	Q12799	Q12799	828
DRC5	DRC7	Q8IY82	818
DRC5	DRC4	O95995	783
DRC5	DRC2	Q8IXS2	779
DRC5	DYNLT1	P63172	761
DRC5	DRC3	Q9H069	712
DRC5	DRC9	Q9H095	708
DRC5	DRC10	Q96DY2	671
DRC5	FBXL13	Q8NEE6	670
DRC5	DRC11	Q86XH1	668
DRC5	TCP1	P17987	635
DRC5	DRC8	Q5VUJ9	591
DRC5	RSPH9	Q9H1X1	587
DRC5	SPATS1	Q496A3	551

IntAct

4 interactions, top by confidence:

A	B	Type	Score
TCTE1	DVL2	psi-mi:“MI:2364”(proximity)	0.270
TCTN3	TMEM120B	psi-mi:“MI:2364”(proximity)	0.270

ESM2 similar proteins: A1A5X2, A2RT62, A6H639, A8Y3R9, B3FL73, D3Z902, D3ZXS4, G5EDB9, O49286, P34284, P87053, Q09299, Q0P4D1, Q0VD31, Q17R01, Q19857, Q32PG9, Q4R642, Q570C0, Q5BJ29, Q5JU00, Q5MJ12, Q65XV2, Q8BFZ4, Q8BH70, Q8BID8, Q8BVU0, Q8C4V4, Q8CDU4, Q8CFJ9, Q8J2J3, Q8LB33, Q8N1E6, Q8N461, Q8W104, Q96S15, Q9EPX5, Q9LPL4, Q9LW29, Q9NXK8

Diamond homologs: A6H639, A8HMZ4, Q4R642, Q5JU00

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
TCTE1	“form complex”	“Nexin-dynein regulatory complex”	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	44
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1075 predictions. Top by Δscore:

Variant	Effect	Δscore
6:44280386:CCGTC:C	acceptor_gain	1.0000
6:44280387:CGTC:C	acceptor_gain	1.0000
6:44280387:CGTCC:C	acceptor_gain	1.0000
6:44280388:GTC:G	acceptor_gain	1.0000
6:44280388:GTCC:G	acceptor_loss	1.0000
6:44280389:TC:T	acceptor_gain	1.0000
6:44280390:CC:C	acceptor_gain	1.0000
6:44280391:C:CC	acceptor_gain	1.0000
6:44280391:C:CG	acceptor_loss	1.0000
6:44280391:C:T	acceptor_gain	1.0000
6:44280392:T:C	acceptor_loss	1.0000
6:44280402:G:C	acceptor_gain	1.0000
6:44280402:G:GC	acceptor_gain	1.0000
6:44285960:GTA:G	donor_loss	1.0000
6:44285961:TAC:T	donor_loss	1.0000
6:44285962:A:AT	donor_loss	1.0000
6:44285963:C:CT	donor_loss	1.0000
6:44280405:C:CT	acceptor_gain	0.9900
6:44282103:GGCTC:G	donor_loss	0.9900
6:44282104:GCT:G	donor_loss	0.9900
6:44282105:CTCAC:C	donor_loss	0.9900
6:44282106:TCACC:T	donor_loss	0.9900
6:44282107:C:CG	donor_loss	0.9900
6:44282108:A:AC	donor_gain	0.9900
6:44282108:ACCAG:A	donor_gain	0.9900
6:44282109:C:CC	donor_gain	0.9900
6:44282109:CCAG:C	donor_gain	0.9900
6:44282109:CCAGC:C	donor_gain	0.9900
6:44282298:G:C	acceptor_gain	0.9900
6:44282559:TCT:T	acceptor_loss	0.9900

AlphaMissense

3269 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:44282290:G:C	N372K	0.981
6:44282290:G:T	N372K	0.981
6:44282206:A:C	N400K	0.980
6:44282206:A:T	N400K	0.980
6:44280374:A:G	L438P	0.979
6:44282539:G:C	S289R	0.974
6:44282539:G:T	S289R	0.974
6:44282541:T:G	S289R	0.974
6:44282122:G:C	N428K	0.972
6:44282122:G:T	N428K	0.972
6:44282186:G:T	A407D	0.972
6:44282270:C:T	G379D	0.967
6:44286042:G:C	F256L	0.965
6:44286042:G:T	F256L	0.965
6:44286044:A:G	F256L	0.965
6:44280374:A:T	L438H	0.964
6:44282300:A:G	L369P	0.963
6:44282374:G:C	N344K	0.963
6:44282374:G:T	N344K	0.963
6:44282132:A:G	L425P	0.959
6:44280374:A:C	L438R	0.957
6:44282455:G:C	N317K	0.957
6:44282455:G:T	N317K	0.957
6:44282187:C:G	A407P	0.956
6:44282201:A:G	L402P	0.956
6:44282231:A:T	L392H	0.953
6:44282354:G:T	A351D	0.953
6:44282216:A:T	L397H	0.951
6:44282306:A:G	L367P	0.951
6:44282216:A:G	L397P	0.950

dbSNP variants (sampled 300 via entrez): RS1000059164 (6:44281244 G>A), RS1000133882 (6:44295190 G>A), RS1000148509 (6:44289123 C>A), RS1000204875 (6:44291764 G>C), RS1000435417 (6:44299689 T>C), RS1000632111 (6:44279795 G>T), RS1000653674 (6:44298678 G>A), RS1000760074 (6:44298480 G>C), RS1000780802 (6:44293355 G>A), RS1000802243 (6:44297913 G>A), RS1000864124 (6:44297527 C>G), RS1000992409 (6:44292197 G>A), RS1001173076 (6:44285783 C>A,T), RS1001280808 (6:44297997 G>A), RS1001508219 (6:44279933 A>G)

Disease associations

OMIM: gene MIM:186975 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST005956_58	Waist-to-hip ratio adjusted for BMI	7.000000e-26
GCST005957_1	Waist-to-hip ratio adjusted for BMI (age <50)	2.000000e-14
GCST005958_2	Waist-to-hip ratio adjusted for BMI (age >50)	2.000000e-19
GCST005962_2	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	3.000000e-31

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

9 total (human), top 9 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
ethyl-p-hydroxybenzoate	decreases expression	1
perfluorooctanoic acid	affects cotreatment, decreases expression	1
perfluorooctane sulfonic acid	affects cotreatment, decreases expression	1
perfluorohexanesulfonic acid	affects cotreatment, decreases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Acrylamide	increases expression	1

Cellosaurus cell lines

1 cell lines: 1 telomerase immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_C3KL	N/Tert-1 TCTE1	Telomerase immortalized cell line	Male

Clinical trials (associated diseases)

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