LRCH3

Summary

LRCH3 (leucine rich repeats and calponin homology domain containing 3, HGNC:28637) is a protein-coding gene on chromosome 3q29, encoding DISP complex protein LRCH3 (Q96II8). As part of the DISP complex, may regulate the association of septins with actin and thereby regulate the actin cytoskeleton.

Involved in septin cytoskeleton organization. Located in cytosol.

Source: NCBI Gene 84859 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 156 total
• MANE Select transcript: NM_001365715

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28637
Approved symbol	LRCH3
Name	leucine rich repeats and calponin homology domain containing 3
Location	3q29
Locus type	gene with protein product
Status	Approved
Aliases	MGC4126
Ensembl gene	ENSG00000186001
Ensembl biotype	protein_coding
Entrez	84859

Gene structure

Transcript identifiers

Ensembl transcripts: 26 — 15 protein_coding, 9 retained_intron, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000334859, ENST00000414675, ENST00000425562, ENST00000428136, ENST00000433298, ENST00000438796, ENST00000441090, ENST00000443727, ENST00000452660, ENST00000461674, ENST00000466054, ENST00000466845, ENST00000471667, ENST00000473177, ENST00000476664, ENST00000481048, ENST00000483442, ENST00000493726, ENST00000494069, ENST00000892268, ENST00000892269, ENST00000926222, ENST00000926223, ENST00000926224, ENST00000926225, ENST00000969020

RefSeq mRNA: 7 — MANE Select: NM_001365715 NM_001363887, NM_001365715, NM_001365716, NM_001365717, NM_001365718, NM_001365719, NM_032773

CCDS: CCDS3330, CCDS87193, CCDS93456

Canonical transcript exons

ENST00000425562 — 21 exons

Exon	Start	End
ENSE00001336723	197829564	197829673
ENSE00001336729	197817176	197817302
ENSE00001336732	197814908	197815052
ENSE00001411563	197847872	197848021
ENSE00001852468	197791254	197791540
ENSE00001910843	197883541	197888436
ENSE00003470573	197854392	197854445
ENSE00003527223	197847409	197847460
ENSE00003534847	197871325	197871462
ENSE00003555294	197865423	197865471
ENSE00003574993	197870160	197870278
ENSE00003576521	197826878	197827014
ENSE00003578741	197820325	197820430
ENSE00003583334	197830770	197830863
ENSE00003597970	197858834	197858905
ENSE00003606731	197852561	197852620
ENSE00003614087	197839321	197839397
ENSE00003632514	197866112	197866219
ENSE00003665961	197835674	197835822
ENSE00003670684	197875698	197875775
ENSE00003683067	197832197	197832317

Expression profiles

Bgee: expression breadth ubiquitous, 267 present calls, max score 96.49.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 30.8636 / max 198.1024, expressed in 1814 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
40779	30.1562	1813
40780	0.6140	318
40782	0.0803	35
40778	0.0131	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	96.49	gold quality
calcaneal tendon	UBERON:0003701	94.12	gold quality
colonic epithelium	UBERON:0000397	94.00	gold quality
secondary oocyte	CL:0000655	93.36	gold quality
oocyte	CL:0000023	92.87	gold quality
corpus callosum	UBERON:0002336	91.16	gold quality
tendon	UBERON:0000043	90.61	gold quality
tibial nerve	UBERON:0001323	90.31	gold quality
adrenal tissue	UBERON:0018303	90.11	gold quality
left ovary	UBERON:0002119	90.08	gold quality
cerebellar cortex	UBERON:0002129	90.08	gold quality
cerebellar hemisphere	UBERON:0002245	90.07	gold quality
right hemisphere of cerebellum	UBERON:0014890	89.98	gold quality
urethra	UBERON:0000057	89.86	gold quality
stromal cell of endometrium	CL:0002255	89.77	gold quality
ventricular zone	UBERON:0003053	89.57	gold quality
right ovary	UBERON:0002118	89.41	gold quality
cerebellum	UBERON:0002037	88.98	gold quality
mucosa of stomach	UBERON:0001199	88.61	gold quality
body of uterus	UBERON:0009853	88.53	gold quality
gastrocnemius	UBERON:0001388	88.19	gold quality
ascending aorta	UBERON:0001496	88.19	gold quality
muscle of leg	UBERON:0001383	88.13	gold quality
thoracic aorta	UBERON:0001515	88.11	gold quality
descending thoracic aorta	UBERON:0002345	88.09	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	88.02	gold quality
ectocervix	UBERON:0012249	87.93	gold quality
ovary	UBERON:0000992	87.84	gold quality
aorta	UBERON:0000947	87.83	gold quality
tonsil	UBERON:0002372	87.77	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-5061	yes	14.86
E-ANND-3	yes	6.61
E-MTAB-7249	no	373.89
E-MTAB-7303	no	150.27

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

12 targeting LRCH3, 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-218-5P	99.93	72.22	2103
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-636	99.80	69.58	1500
HSA-MIR-4804-3P	99.65	67.78	866
HSA-MIR-4502	99.65	66.99	1021
HSA-MIR-6737-3P	98.95	68.56	1577
HSA-MIR-7157-3P	98.95	68.70	1582
HSA-MIR-5008-3P	98.73	67.50	1433
HSA-MIR-4720-3P	98.50	68.88	988
HSA-MIR-654-3P	98.38	67.61	905

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	lrch3	ENSDARG00000100679
mus_musculus	Lrch3	ENSMUSG00000022801
rattus_norvegicus	Lrch3	ENSRNOG00000001774
drosophila_melanogaster	Lrch	FBGN0032633

Paralogs (31): LRRC7 (ENSG00000033122), PHLPP2 (ENSG00000040199), LRRC40 (ENSG00000066557), LRCH4 (ENSG00000077454), PHLPP1 (ENSG00000081913), SHOC2 (ENSG00000108061), ERBIN (ENSG00000112851), LRRC39 (ENSG00000122477), LRCH2 (ENSG00000130224), LRCH1 (ENSG00000136141), LRRC8A (ENSG00000136802), LRRC1 (ENSG00000137269), MFHAS1 (ENSG00000147324), LRRC27 (ENSG00000148814), LRRK1 (ENSG00000154237), LRRC58 (ENSG00000163428), LRRC2 (ENSG00000163827), LRRC18 (ENSG00000165383), LRRC28 (ENSG00000168904), LRRC8E (ENSG00000171017), LRRC8C (ENSG00000171488), LRRC8D (ENSG00000171492), PIDD1 (ENSG00000177595), SCRIB (ENSG00000180900), LRRIQ4 (ENSG00000188306), LRRC8B (ENSG00000197147), LRRC10 (ENSG00000198812), LRRC10B (ENSG00000204950), LRRC30 (ENSG00000206422), LRRC69 (ENSG00000214954), LRRD1 (ENSG00000240720)

Protein

Protein identifiers

DISP complex protein LRCH3 — Q96II8 (reviewed: Q96II8)

Alternative names: Leucine-rich repeat and calponin homology domain-containing protein 3

All UniProt accessions (5): E9PD99, Q96II8, F8WFB5, H7C0J8, H7C1G3

UniProt curated annotations — full annotation on UniProt →

Function. As part of the DISP complex, may regulate the association of septins with actin and thereby regulate the actin cytoskeleton.

Subunit / interactions. Component of the DOCK7-induced septin displacement/DISP complex, at least composed of DOCK7, LRCH3 and MYO6.

Subcellular location. Cytoplasm.

Isoforms (4)

UniProt ID	Names	Canonical?
Q96II8-1	1	yes
Q96II8-2	2
Q96II8-3	3
Q96II8-4	4

RefSeq proteins (7): NP_001350816, NP_001352644, NP_001352645, NP_001352646, NP_001352647, NP_001352648, NP_116162 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001611	Leu-rich_rpt	Repeat
IPR001715	CH_dom	Domain
IPR003591	Leu-rich_rpt_typical-subtyp	Repeat
IPR032675	LRR_dom_sf	Homologous_superfamily
IPR036872	CH_dom_sf	Homologous_superfamily
IPR050216	LRR_domain-containing	Family

Pfam: PF00307, PF13855

UniProt features (27 total): repeat 10, modified residue 5, region of interest 4, splice variant 4, chain 1, domain 1, compositionally biased region 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96II8-F1	66.13	0.37

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 (5): 324, 415, 419, 611, 628

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 80 (showing top): CHANDRAN_METASTASIS_UP, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_DN, TURASHVILI_BREAST_NORMAL_DUCTAL_VS_LOBULAR_UP, JOHNSTONE_PARVB_TARGETS_3_DN, PURBEY_TARGETS_OF_CTBP1_AND_SATB1_DN, PEDERSEN_METASTASIS_BY_ERBB2_ISOFORM_7, WAKABAYASHI_ADIPOGENESIS_PPARG_BOUND_8D, GSE14699_NAIVE_VS_ACT_CD8_TCELL_DN, CBX7_TARGET_GENES, CIITA_TARGET_GENES, FEV_TARGET_GENES, HMGA1_TARGET_GENES, NFKBIA_TARGET_GENES, PAX3_TARGET_GENES, SETD7_TARGET_GENES

GO Biological Process (1): septin cytoskeleton organization (GO:0032185)

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

GO Cellular Component (2): cytoplasm (GO:0005737), cytosol (GO:0005829)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
cytoskeleton organization	1
binding	1
intracellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

1689 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LRCH3	DOCK7	Q96N67	847
LRCH3	MYO6	Q9UM54	605
LRCH3	DOCK8	Q8NF50	602
LRCH3	DOCK6	Q96HP0	464
LRCH3	ZDHHC19	Q8WVZ1	454
LRCH3	MYH6	P13533	434
LRCH3	RAI14	Q9P0K7	427
LRCH3	ZDHHC14	Q8IZN3	418
LRCH3	TRA2B	P62995	400
LRCH3	PYROXD2	Q8N2H3	399
LRCH3	SMTNL2	Q2TAL5	397
LRCH3	ARHGAP4	P98171	392
LRCH3	ANKRD28	O15084	391
LRCH3	TPD52L2	O43399	383
LRCH3	PPP6R1	Q9UPN7	382

IntAct

95 interactions, top by confidence:

A	B	Type	Score
LRCH3	DOCK7	psi-mi:“MI:0914”(association)	0.840
LRCH3	DOCK7	psi-mi:“MI:0915”(physical association)	0.840
DOCK7	LRCH3	psi-mi:“MI:0914”(association)	0.840
LRCH3	DOCK7	psi-mi:“MI:0403”(colocalization)	0.840
DOCK8	LRCH2	psi-mi:“MI:0914”(association)	0.740
MYO6	LRCH3	psi-mi:“MI:0915”(physical association)	0.730
LRCH3	DOCK6	psi-mi:“MI:0914”(association)	0.730
MYO6	GIPC1	psi-mi:“MI:0914”(association)	0.690
MOB1A	LATS1	psi-mi:“MI:0914”(association)	0.670
LRCH3	DOCK8	psi-mi:“MI:0915”(physical association)	0.560
LRCH3	LRCH2	psi-mi:“MI:0914”(association)	0.530
DOCK7	LRCH2	psi-mi:“MI:0914”(association)	0.530
DCAF7	CLASP2	psi-mi:“MI:0914”(association)	0.510
MOB1B	PPP6C	psi-mi:“MI:2364”(proximity)	0.480
LRCH3	MYO6	psi-mi:“MI:0915”(physical association)	0.450
MOB1A	PPP6C	psi-mi:“MI:2364”(proximity)	0.420
MOB1A	PPP6C	psi-mi:“MI:0914”(association)	0.420
LRCH3	DOCK7	psi-mi:“MI:0915”(physical association)	0.400
	LRCH3	psi-mi:“MI:0915”(physical association)	0.400
Tuba3a	CCHCR1	psi-mi:“MI:0914”(association)	0.350
PARD6B	PARD3	psi-mi:“MI:0914”(association)	0.350
PARD6A		psi-mi:“MI:0914”(association)	0.350
Cdca8	NAP1L1	psi-mi:“MI:0914”(association)	0.350

BioGRID (170): LRCH3 (Two-hybrid), LRCH3 (Affinity Capture-MS), LRCH3 (Affinity Capture-MS), LRCH3 (Affinity Capture-MS), LRCH3 (Affinity Capture-MS), LRCH3 (Affinity Capture-MS), LRCH3 (Affinity Capture-MS), LRCH3 (Affinity Capture-MS), LRCH3 (Affinity Capture-MS), LRCH3 (Affinity Capture-MS), LRCH3 (Affinity Capture-MS), LRCH3 (Affinity Capture-MS), DOCK8 (Affinity Capture-MS), DOCK6 (Affinity Capture-MS), DOCK7 (Affinity Capture-MS)

ESM2 similar proteins: A0JM56, A2RRS8, A6H759, A6NJI9, A6PVS8, B0FXQ5, B1ANS9, B7FF12, D3ZXS4, D4A039, E9QA62, F1MCA7, O00522, P62046, P70587, Q0V9Y8, Q0VAK6, Q14DL3, Q3U3V8, Q3UMG5, Q3V0L5, Q4KLV2, Q5JTW2, Q5PPX0, Q5SUS0, Q5VUJ6, Q6AXZ2, Q6AYL8, Q6GQN5, Q6IRU7, Q6P5J6, Q7Z3E5, Q7ZV84, Q80TE7, Q80TM9, Q8BGI7, Q8BVU0, Q8C008, Q8C0Q4, Q8C5W4

Diamond homologs: O75427, P26932, P41737, P52735, P62046, Q3UMG5, Q5S006, Q5VUJ6, Q60992, Q6Z8P4, Q8BVU0, Q921G6, Q96II8, Q9R0C8, Q9Y2L9, P15498, P27870, P54100, Q08DN7, Q24799, Q960C5, Q55E58, Q8BXA7, Q8WWI1, Q9UKW4, P37803, Q9NHV9

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 103 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
microtubule cytoskeleton organization	6	8.1×	7e-03
actin filament organization	6	7.9×	7e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	103
Likely benign	19
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

4557 predictions. Top by Δscore:

Variant	Effect	Δscore
3:197791488:G:GT	donor_gain	1.0000
3:197814903:TTTA:T	acceptor_loss	1.0000
3:197814904:TTAG:T	acceptor_loss	1.0000
3:197814905:TAG:T	acceptor_loss	1.0000
3:197814906:A:AG	acceptor_gain	1.0000
3:197814906:AG:A	acceptor_loss	1.0000
3:197814907:G:GG	acceptor_gain	1.0000
3:197814907:GACCT:G	acceptor_gain	1.0000
3:197815049:TTAGG:T	donor_loss	1.0000
3:197815050:TAGGT:T	donor_loss	1.0000
3:197815051:AGGTA:A	donor_loss	1.0000
3:197815052:GGTAA:G	donor_loss	1.0000
3:197815053:G:C	donor_loss	1.0000
3:197815053:G:GG	donor_gain	1.0000
3:197815054:T:A	donor_loss	1.0000
3:197817174:A:AG	acceptor_gain	1.0000
3:197817175:G:GA	acceptor_gain	1.0000
3:197817175:GTC:G	acceptor_gain	1.0000
3:197817303:G:GG	donor_gain	1.0000
3:197817541:A:T	donor_gain	1.0000
3:197820317:C:CA	acceptor_gain	1.0000
3:197826876:A:AG	acceptor_gain	1.0000
3:197826877:G:GA	acceptor_gain	1.0000
3:197826877:GA:G	acceptor_gain	1.0000
3:197829563:GAT:G	acceptor_gain	1.0000
3:197829563:GATAT:G	acceptor_gain	1.0000
3:197830764:C:CA	acceptor_gain	1.0000
3:197830768:A:AG	acceptor_gain	1.0000
3:197830769:G:GA	acceptor_gain	1.0000
3:197830769:GC:G	acceptor_gain	1.0000

AlphaMissense

5021 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:197871386:G:A	G685D	1.000
3:197871431:T:A	V700D	1.000
3:197814921:T:A	N92K	0.999
3:197814921:T:G	N92K	0.999
3:197814990:T:A	N115K	0.999
3:197814990:T:G	N115K	0.999
3:197817182:C:A	N138K	0.999
3:197817182:C:G	N138K	0.999
3:197826990:T:A	N251K	0.999
3:197826990:T:G	N251K	0.999
3:197829601:T:C	L272P	0.999
3:197830819:T:C	F313L	0.999
3:197830821:C:A	F313L	0.999
3:197830821:C:G	F313L	0.999
3:197830825:A:C	S315R	0.999
3:197830827:T:A	S315R	0.999
3:197830827:T:G	S315R	0.999
3:197870274:G:C	R663P	0.999
3:197871377:T:C	L682P	0.999
3:197871385:G:C	G685R	0.999
3:197871386:G:T	G685V	0.999
3:197871395:T:A	L688H	0.999
3:197871397:T:C	C689R	0.999
3:197871398:G:A	C689Y	0.999
3:197871399:C:G	C689W	0.999
3:197871404:T:C	L691S	0.999
3:197871407:C:A	A692D	0.999
3:197871440:T:A	I703N	0.999
3:197871446:T:A	V705D	0.999
3:197871449:C:A	P706H	0.999

dbSNP variants (sampled 300 via entrez): RS1000000626 (3:197880933 T>A), RS1000022948 (3:197830240 A>G), RS1000037273 (3:197808313 C>G), RS1000062099 (3:197853189 T>C), RS1000071366 (3:197830571 A>G), RS1000094870 (3:197880441 T>C), RS1000098991 (3:197840260 A>G), RS1000121721 (3:197798454 G>C), RS1000140431 (3:197854660 A>G), RS1000211223 (3:197845359 G>A,T), RS1000240776 (3:197804590 T>C), RS1000286917 (3:197881334 C>G,T), RS1000311829 (3:197844494 G>C), RS1000384649 (3:197812021 T>A), RS1000388820 (3:197856467 G>A)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST002724_5	Airway responsiveness in chronic obstructive pulmonary disease	7.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0006897	airway responsiveness measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, increases expression, increases methylation	5
sodium arsenite	affects expression, decreases expression, affects cotreatment, increases abundance	3
bisphenol A	decreases expression, increases methylation	2
Arsenic	affects methylation, affects cotreatment, decreases expression, increases abundance	2
Benzo(a)pyrene	decreases expression, increases methylation	2
FR900359	decreases phosphorylation	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
pirinixic acid	affects binding, increases activity, increases expression	1
beta-lapachone	increases expression	1
arsenite	affects binding, decreases reaction	1
afimoxifene	decreases reaction, decreases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluoro-n-nonanoic acid	increases expression	1
perfluorohexanesulfonic acid	increases expression	1
abrine	increases expression	1
Irinotecan	decreases expression	1
Acetaminophen	increases expression	1
Demecolcine	increases expression	1
Estrogens	decreases expression, decreases reaction	1
Formaldehyde	decreases expression	1
Ivermectin	decreases expression	1
Manganese	affects cotreatment, decreases expression, increases abundance	1
Silicon Dioxide	increases expression	1
Thiram	decreases expression	1
Vincristine	increases expression	1
Antirheumatic Agents	increases expression	1

Clinical trials (associated diseases)

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