LRRCC1

Summary

LRRCC1 (leucine rich repeat and coiled-coil centrosomal protein 1, HGNC:29373) is a protein-coding gene on chromosome 8q21.2, encoding Leucine-rich repeat and coiled-coil domain-containing protein 1 (Q9C099). Required for the organization of the mitotic spindle.

This gene encodes a centrosomal protein that maintains the structural integrity of the centrosome and plays a key role in mitotic spindle formation. The encoded protein contains an N-terminal leucine-rich repeat domain and a C-terminal coiled-coil domain. It associates with the centrosome throughout the cell cycle and accumulates on the mitotic centrosome.

Source: NCBI Gene 85444 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 234 total — 1 pathogenic
• MANE Select transcript: NM_033402

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29373
Approved symbol	LRRCC1
Name	leucine rich repeat and coiled-coil centrosomal protein 1
Location	8q21.2
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1764, CLERC, VFL1
Ensembl gene	ENSG00000133739
Ensembl biotype	protein_coding
OMIM	617791
Entrez	85444

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 5 protein_coding, 4 nonsense_mediated_decay

ENST00000360375, ENST00000414626, ENST00000517875, ENST00000522567, ENST00000522770, ENST00000523669, ENST00000926003, ENST00000926004, ENST00000962243

RefSeq mRNA: 5 — MANE Select: NM_033402 NM_001349636, NM_001349637, NM_001349638, NM_001349639, NM_033402

CCDS: CCDS43750

Canonical transcript exons

ENST00000360375 — 19 exons

Exon	Start	End
ENSE00000980887	85109595	85109800
ENSE00001618653	85141382	85141517
ENSE00001635430	85138338	85138475
ENSE00001637346	85138035	85138243
ENSE00002097998	85107238	85107399
ENSE00003489505	85131760	85131961
ENSE00003506824	85137464	85137627
ENSE00003517553	85129919	85130058
ENSE00003534793	85112932	85113099
ENSE00003535863	85115100	85115275
ENSE00003562542	85124792	85124939
ENSE00003569313	85110115	85110180
ENSE00003637502	85134847	85135032
ENSE00003651602	85126689	85126837
ENSE00003656368	85123413	85123606
ENSE00003660129	85135789	85135963
ENSE00003680794	85129175	85129379
ENSE00003685241	85115375	85115584
ENSE00003841504	85145389	85146080

Expression profiles

Bgee: expression breadth ubiquitous, 189 present calls, max score 92.33.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.2878 / max 141.8241, expressed in 1514 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
89591	6.6161	1496
89592	0.6717	346

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	92.33	gold quality
ventricular zone	UBERON:0003053	90.31	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	86.60	gold quality
left testis	UBERON:0004533	84.89	gold quality
rectum	UBERON:0001052	84.83	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.41	gold quality
right testis	UBERON:0004534	84.38	gold quality
ganglionic eminence	UBERON:0004023	84.28	gold quality
testis	UBERON:0000473	83.72	gold quality
spinal cord	UBERON:0002240	83.58	gold quality
sural nerve	UBERON:0015488	82.65	gold quality
ileal mucosa	UBERON:0000331	82.61	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	81.29	gold quality
popliteal artery	UBERON:0002250	80.62	gold quality
tibial artery	UBERON:0007610	80.61	gold quality
cortical plate	UBERON:0005343	80.60	gold quality
tibial nerve	UBERON:0001323	80.55	gold quality
colonic epithelium	UBERON:0000397	80.47	gold quality
amygdala	UBERON:0001876	80.35	gold quality
smooth muscle tissue	UBERON:0001135	79.90	gold quality
descending thoracic aorta	UBERON:0002345	79.79	gold quality
muscle layer of sigmoid colon	UBERON:0035805	79.46	gold quality
aorta	UBERON:0000947	79.43	gold quality
hypothalamus	UBERON:0001898	79.16	gold quality
left coronary artery	UBERON:0001626	78.80	gold quality
putamen	UBERON:0001874	78.34	gold quality
thoracic aorta	UBERON:0001515	78.32	gold quality
ascending aorta	UBERON:0001496	78.11	gold quality
right coronary artery	UBERON:0001625	77.79	gold quality
left ovary	UBERON:0002119	77.71	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.34

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

45 targeting LRRCC1, 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-3163	100.00	77.23	8605
HSA-MIR-340-5P	100.00	72.50	4437
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-10523-5P	99.91	69.22	2038
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-221-3P	99.86	71.56	1329
HSA-MIR-222-3P	99.86	71.35	1337
HSA-MIR-576-5P	99.84	70.46	2582
HSA-MIR-2681-5P	99.75	67.64	1655
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-105-5P	99.54	69.24	2060
HSA-MIR-7853-5P	99.54	69.30	2055
HSA-MIR-7159-5P	99.53	72.12	2472
HSA-MIR-12123	99.52	71.79	2990
HSA-MIR-154-3P	99.50	70.05	831
HSA-MIR-487A-3P	99.50	69.95	840
HSA-MIR-203A-3P	99.49	70.56	2806
HSA-MIR-16-2-3P	99.29	70.60	1954

Literature-anchored findings (GeneRIF, showing 2)

• These data indicate that the major function of CLERC during mitosis is to maintain the structural integrity of centrosomes, thereby contributing to spindle bipolarity. (PMID:18728398)
• Evolutionary conservation of centriole rotational asymmetry in the human centrosome. (PMID:35319462)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	lrrcc1	ENSDARG00000078535
mus_musculus	Lrrcc1	ENSMUSG00000027550
rattus_norvegicus	Lrrcc1	ENSRNOG00000010891
drosophila_melanogaster	TbCMF46	FBGN0032163
drosophila_melanogaster	Ppr-Y	FBGN0046697

Paralogs (13): LRRC23 (ENSG00000010626), LRRC61 (ENSG00000127399), DNAAF11 (ENSG00000129295), LRRC9 (ENSG00000131951), LRRC49 (ENSG00000137821), LRRC46 (ENSG00000141294), DNAAF1 (ENSG00000154099), LRGUK (ENSG00000155530), LRRC43 (ENSG00000158113), LRRIQ3 (ENSG00000162620), DRC3 (ENSG00000171962), PPP1R42 (ENSG00000178125), CEP97 (ENSG00000182504)

Protein

Protein identifiers

Leucine-rich repeat and coiled-coil domain-containing protein 1 — Q9C099 (reviewed: Q9C099)

Alternative names: Centrosomal leucine-rich repeat and coiled-coil domain-containing protein

All UniProt accessions (3): E5RGA4, E5RI08, Q9C099

UniProt curated annotations — full annotation on UniProt →

Function. Required for the organization of the mitotic spindle. Maintains the structural integrity of centrosomes during mitosis.

Subcellular location. Cytoplasm. Cytoskeleton. Microtubule organizing center. Centrosome. Centriole.

Similarity. Belongs to the LRRCC1 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9C099-1	1	yes
Q9C099-2	2

RefSeq proteins (5): NP_001336565, NP_001336566, NP_001336567, NP_001336568, NP_208325* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001611	Leu-rich_rpt	Repeat
IPR025875	Leu-rich_rpt_4	Repeat
IPR032675	LRR_dom_sf	Homologous_superfamily

Pfam: PF12799

UniProt features (20 total): sequence conflict 6, repeat 5, sequence variant 3, chain 1, splice variant 1, domain 1, region of interest 1, coiled-coil region 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9C099-F1	74.43	0.35

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 95 (showing top): GOZGIT_ESR1_TARGETS_DN, MODULE_308, GOCC_MICROTUBULE_ORGANIZING_CENTER, GOCC_CENTROSOME, FISCHER_DREAM_TARGETS, GOCC_CENTRIOLE, NUYTTEN_EZH2_TARGETS_DN, GOBP_CELL_DIVISION, GEORGES_TARGETS_OF_MIR192_AND_MIR215, chr8q21, KOYAMA_SEMA3B_TARGETS_DN, PLASARI_TGFB1_TARGETS_10HR_DN, RAO_BOUND_BY_SALL4_ISOFORM_B, TASOR_TARGET_GENES, ZNF581_TARGET_GENES

GO Biological Process (1): cell division (GO:0051301)

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

GO Cellular Component (4): cytoplasm (GO:0005737), centrosome (GO:0005813), centriole (GO:0005814), cytoskeleton (GO:0005856)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
microtubule organizing center	2
intracellular membraneless organelle	2
cellular process	1
binding	1
intracellular anatomical structure	1
cellular anatomical structure	1
centriole	1

Protein interactions and networks

STRING

993 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LRRCC1	TMEM89	A2RUT3	667
LRRCC1	CCDC61	Q9Y6R9	586
LRRCC1	IQCF5	A8MTL0	557
LRRCC1	RBIS	Q8N0T1	529
LRRCC1	CEP83	Q9Y592	486
LRRCC1	FAM174C	Q9BVV8	482
LRRCC1	FAM98C	Q17RN3	479
LRRCC1	RALYL	Q86SE5	449
LRRCC1	NSMCE2	Q96MF7	448
LRRCC1	MRAS	O14807	423
LRRCC1	SPATA31F1	Q6ZU69	419
LRRCC1	CNTLN	Q9NXG0	419
LRRCC1	PLEKHM3	Q6ZWE6	406
LRRCC1	TMEM184A	Q6ZMB5	404
LRRCC1	SLC7A13	Q8TCU3	402

IntAct

26 interactions, top by confidence:

A	B	Type	Score
SKA3	CCDC85C	psi-mi:“MI:0914”(association)	0.530
LRRCC1	NS	psi-mi:“MI:0915”(physical association)	0.370
NS	LRRCC1	psi-mi:“MI:0915”(physical association)	0.370
LRRCC1	NS1	psi-mi:“MI:0915”(physical association)	0.370
	LRRCC1	psi-mi:“MI:0915”(physical association)	0.370
RYBP	FAM186A	psi-mi:“MI:0914”(association)	0.350
LRRCC1	MYH7B	psi-mi:“MI:0914”(association)	0.350
ANKRD13A	DCK	psi-mi:“MI:0914”(association)	0.350
NXT2	MYO1G	psi-mi:“MI:0914”(association)	0.350
PCM1	CCDC66	psi-mi:“MI:2364”(proximity)	0.270
TRAF3IP1	LRRCC1	psi-mi:“MI:0915”(physical association)	0.000
DISC1	LRRCC1	psi-mi:“MI:0915”(physical association)	0.000
CDC5L	LRRCC1	psi-mi:“MI:0915”(physical association)	0.000
LRRCC1		psi-mi:“MI:0915”(physical association)	0.000
	LRRCC1	psi-mi:“MI:0915”(physical association)	0.000
LRRCC1	aer	psi-mi:“MI:0915”(physical association)	0.000
flaV	LRRCC1	psi-mi:“MI:0915”(physical association)	0.000
LRRCC1	ORF90	psi-mi:“MI:0915”(physical association)	0.000
NRIP1	LRRCC1	psi-mi:“MI:0915”(physical association)	0.000
LRRCC1	C14orf119	psi-mi:“MI:0915”(physical association)	0.000
LRRCC1	CAPNS1	psi-mi:“MI:0915”(physical association)	0.000
LRRCC1	FADD	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (46): LRRCC1 (Proximity Label-MS), MYH7B (Affinity Capture-MS), ACTN3 (Affinity Capture-MS), PCM1 (Affinity Capture-MS), CEP131 (Affinity Capture-MS), ATP1A4 (Affinity Capture-MS), ATP2A3 (Affinity Capture-MS), POTEE (Affinity Capture-MS), ATP2A1 (Affinity Capture-MS), PIBF1 (Affinity Capture-MS), LRRCC1 (Affinity Capture-MS), TUBA3C (Affinity Capture-MS), KIF7 (Affinity Capture-MS), MIB1 (Affinity Capture-MS), STRIP1 (Affinity Capture-MS)

ESM2 similar proteins: A1Z8P9, A2ZAC2, A4GSN8, B3DLE8, F1MA98, F4I9A2, F6ZDS4, G5E861, O15078, O46480, P0CB23, P12270, P16568, P85001, P93203, Q0DY81, Q0WVL7, Q10PZ6, Q336R3, Q498G2, Q4I7N9, Q4WDD7, Q5BIX7, Q5BJF6, Q5EE04, Q5M9N0, Q5TZ80, Q5ZJ27, Q5ZKK5, Q66GS9, Q66KE8, Q6A078, Q6AYX5, Q6NRC9, Q6P5D4, Q84VY2, Q84WU4, Q8BIL5, Q8CJ99, Q8GYX3

Diamond homologs: Q69ZB0, Q6NRC9, Q9C099

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	147
Likely benign	41
Benign	20

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
266077	NM_033402.5(LRRCC1):c.105-1G>C	Pathogenic

SpliceAI

2864 predictions. Top by Δscore:

Variant	Effect	Δscore
8:85107368:G:GT	donor_gain	1.0000
8:85107368:G:T	donor_gain	1.0000
8:85109593:A:AG	acceptor_gain	1.0000
8:85109594:G:GG	acceptor_gain	1.0000
8:85109594:GC:G	acceptor_gain	1.0000
8:85109719:A:AG	donor_gain	1.0000
8:85110178:GTG:G	donor_gain	1.0000
8:85110178:GTGGT:G	donor_loss	1.0000
8:85110179:TGG:T	donor_loss	1.0000
8:85110181:G:GG	donor_gain	1.0000
8:85110181:GTAA:G	donor_loss	1.0000
8:85110182:TA:T	donor_loss	1.0000
8:85110183:AAGTA:A	donor_loss	1.0000
8:85115582:G:GT	donor_gain	1.0000
8:85115585:G:GG	donor_gain	1.0000
8:85124790:A:AG	acceptor_gain	1.0000
8:85124791:G:GA	acceptor_gain	1.0000
8:85124791:GTT:G	acceptor_gain	1.0000
8:85124791:GTTGT:G	acceptor_gain	1.0000
8:85126687:A:AG	acceptor_gain	1.0000
8:85126688:G:GG	acceptor_gain	1.0000
8:85126688:GTC:G	acceptor_gain	1.0000
8:85126688:GTCC:G	acceptor_gain	1.0000
8:85126688:GTCCC:G	acceptor_gain	1.0000
8:85131745:T:G	acceptor_gain	1.0000
8:85131958:AGAT:A	donor_gain	1.0000
8:85131959:GAT:G	donor_gain	1.0000
8:85131959:GATG:G	donor_gain	1.0000
8:85131962:G:GG	donor_gain	1.0000
8:85132002:G:GG	donor_gain	1.0000

AlphaMissense

6920 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:85134953:T:C	L692P	0.998
8:85109705:T:C	L72P	0.996
8:85109781:T:A	N97K	0.996
8:85109781:T:G	N97K	0.996
8:85109699:T:C	L70P	0.994
8:85109705:T:A	L72Q	0.994
8:85109765:T:C	L92S	0.994
8:85109714:A:T	N75I	0.993
8:85109720:T:C	I77T	0.993
8:85109780:A:T	N97I	0.993
8:85110161:C:A	N119K	0.993
8:85110161:C:G	N119K	0.993
8:85113052:T:C	L166P	0.993
8:85109715:T:A	N75K	0.992
8:85109715:T:G	N75K	0.992
8:85110145:T:C	L114P	0.991
8:85138354:T:A	W907R	0.991
8:85138354:T:C	W907R	0.991
8:85138385:T:C	L917P	0.991
8:85109705:T:G	L72R	0.990
8:85109771:T:C	L94S	0.990
8:85109779:A:T	N97Y	0.990
8:85138439:T:C	L935P	0.990
8:85109639:T:C	L50P	0.989
8:85110136:T:C	L111P	0.989
8:85113080:T:A	N175K	0.989
8:85113080:T:G	N175K	0.989
8:85115136:T:A	L194H	0.989
8:85131944:G:C	A651P	0.989
8:85110160:A:T	N119I	0.988

dbSNP variants (sampled 300 via entrez): RS1000039467 (8:85112506 G>A), RS1000196525 (8:85120061 T>G), RS1000411185 (8:85130465 G>C), RS1000463449 (8:85130873 G>C), RS1000471923 (8:85127003 A>C,G), RS1000530545 (8:85118171 C>A,T), RS1000559337 (8:85112934 T>C), RS1000613653 (8:85125559 G>C), RS1000645002 (8:85118762 A>G), RS1000683565 (8:85123619 G>C), RS1000690451 (8:85125278 C>T), RS1000758115 (8:85126693 T>C), RS1000800010 (8:85132841 A>G), RS1000851939 (8:85110147 A>T), RS1001070531 (8:85117881 C>A)

Disease associations

OMIM: gene MIM:617791 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): Joubert syndrome and related disorders (MONDO:0015369)

Orphanet (1): Joubert syndrome and related disorders (Orphanet:140874)

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST009391_218	Metabolite levels	9.000000e-06
GCST009391_873	Metabolite levels	8.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0010535	sucrose 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
Acetaminophen	decreases expression, increases expression	3
Valproic Acid	affects expression, increases expression	3
potassium chromate(VI)	affects cotreatment, decreases expression	2
Benzo(a)pyrene	affects methylation, decreases expression	2
Tobacco Smoke Pollution	affects expression, decreases expression	2
Tretinoin	decreases expression, increases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	decreases expression	1
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
benzo(e)pyrene	decreases methylation	1
aflatoxin B2	decreases methylation	1
beta-methylcholine	affects expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
chromium hexavalent ion	decreases expression	1
perfluorooctane sulfonic acid	decreases expression	1
abrine	decreases expression	1
(+)-JQ1 compound	decreases expression	1
Temozolomide	increases expression	1
Vorinostat	increases expression	1
Arsenic	affects methylation	1
Cisplatin	increases expression	1
Methapyrilene	decreases methylation	1
Tetrachlorodibenzodioxin	decreases expression	1
Urethane	decreases expression	1
Vincristine	decreases expression	1
Cyclosporine	decreases expression	1
Gold Compounds	decreases expression	1
Cadmium Chloride	decreases expression	1

Clinical trials (associated diseases)

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