LRRC39

Summary

LRRC39 (leucine rich repeat containing 39, HGNC:28228) is a protein-coding gene on chromosome 1p21.2, encoding Leucine-rich repeat-containing protein 39 (Q96DD0). Component of the sarcomeric M-band which plays a role in myocyte response to biomechanical stress.

Predicted to be involved in intracellular signal transduction. Predicted to be located in M band.

Source: NCBI Gene 127495 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 77 total
• MANE Select transcript: NM_144620

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28228
Approved symbol	LRRC39
Name	leucine rich repeat containing 39
Location	1p21.2
Locus type	gene with protein product
Status	Approved
Aliases	MGC14816, myomasp
Ensembl gene	ENSG00000122477
Ensembl biotype	protein_coding
Entrez	127495

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 9 protein_coding

ENST00000342895, ENST00000370137, ENST00000370138, ENST00000853203, ENST00000853204, ENST00000853205, ENST00000962771, ENST00000962772, ENST00000962773

RefSeq mRNA: 4 — MANE Select: NM_144620 NM_001256385, NM_001256386, NM_001256387, NM_144620

CCDS: CCDS58014, CCDS766

Canonical transcript exons

ENST00000370137 — 10 exons

Exon	Start	End
ENSE00000831286	100158231	100158367
ENSE00000831287	100159259	100159415
ENSE00001028850	100160466	100160571
ENSE00001067730	100155051	100155203
ENSE00001067731	100152385	100152524
ENSE00001067733	100156172	100156317
ENSE00001167907	100168404	100168594
ENSE00001451915	100173331	100173370
ENSE00003681662	100148448	100149097
ENSE00003900749	100178135	100178256

Expression profiles

Bgee: expression breadth ubiquitous, 191 present calls, max score 99.37.

FANTOM5 (CAGE): breadth broad, TPM avg 1.4943 / max 179.4404, expressed in 195 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
13511	1.2105	172
13510	0.1609	60
13509	0.0811	44
13512	0.0419	21

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
vastus lateralis	UBERON:0001379	99.37	gold quality
biceps brachii	UBERON:0001507	99.29	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	99.23	gold quality
quadriceps femoris	UBERON:0001377	99.15	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	98.92	gold quality
left ventricle myocardium	UBERON:0006566	98.68	gold quality
deltoid	UBERON:0001476	98.55	gold quality
hindlimb stylopod muscle	UBERON:0004252	98.42	gold quality
skeletal muscle tissue	UBERON:0001134	98.16	gold quality
myocardium	UBERON:0002349	97.87	gold quality
cardiac muscle of right atrium	UBERON:0003379	97.63	gold quality
heart right ventricle	UBERON:0002080	97.16	gold quality
tibialis anterior	UBERON:0001385	96.41	gold quality
apex of heart	UBERON:0002098	95.70	gold quality
gastrocnemius	UBERON:0001388	95.48	gold quality
muscle of leg	UBERON:0001383	95.10	gold quality
cardiac ventricle	UBERON:0002082	94.68	gold quality
heart left ventricle	UBERON:0002084	94.68	gold quality
muscle tissue	UBERON:0002385	94.50	gold quality
body of tongue	UBERON:0011876	94.24	gold quality
cardiac atrium	UBERON:0002081	93.33	gold quality
right atrium auricular region	UBERON:0006631	93.14	gold quality
heart	UBERON:0000948	91.49	gold quality
sperm	CL:0000019	85.92	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.78	gold quality
tongue	UBERON:0001723	84.13	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	82.42	gold quality
right adrenal gland cortex	UBERON:0035827	81.45	gold quality
left adrenal gland	UBERON:0001234	79.50	gold quality
right adrenal gland	UBERON:0001233	79.01	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.73

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

51 targeting LRRC39, 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-3613-3P	100.00	76.36	7965
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-9718	99.94	68.91	918
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-7978	99.86	66.90	856
HSA-MIR-6079	99.84	68.54	1170
HSA-MIR-5010-3P	99.83	70.60	2357
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-2052	99.79	69.37	2031
HSA-MIR-4517	99.76	69.19	1867
HSA-MIR-132-3P	99.73	70.56	1424
HSA-MIR-212-3P	99.73	70.65	1424
HSA-MIR-1303	99.65	69.77	1662
HSA-MIR-6083	99.47	68.73	2393
HSA-MIR-3123	99.47	67.15	2693
HSA-MIR-208A-5P	99.42	70.83	1913
HSA-MIR-208B-5P	99.42	70.83	1952

Literature-anchored findings (GeneRIF, showing 1)

• Reveal myomasp/LRRC39 as a previously unrecognized component of an M-band-associated signaling pathway that regulates cardiomyocyte gene expression in response to biomechanical stress. (PMID:20847312)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	lrrc39	ENSDARG00000071465
mus_musculus	Lrrc39	ENSMUSG00000027961
rattus_norvegicus	Lrrc39	ENSRNOG00000015117

Paralogs (31): LRRC7 (ENSG00000033122), PHLPP2 (ENSG00000040199), LRRC40 (ENSG00000066557), LRCH4 (ENSG00000077454), PHLPP1 (ENSG00000081913), SHOC2 (ENSG00000108061), ERBIN (ENSG00000112851), 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), LRCH3 (ENSG00000186001), LRRIQ4 (ENSG00000188306), LRRC8B (ENSG00000197147), LRRC10 (ENSG00000198812), LRRC10B (ENSG00000204950), LRRC30 (ENSG00000206422), LRRC69 (ENSG00000214954), LRRD1 (ENSG00000240720)

Protein

Protein identifiers

Leucine-rich repeat-containing protein 39 — Q96DD0 (reviewed: Q96DD0)

Alternative names: Myosin-interacting M-band-associated stress-responsive protein

All UniProt accessions (1): Q96DD0

UniProt curated annotations — full annotation on UniProt →

Function. Component of the sarcomeric M-band which plays a role in myocyte response to biomechanical stress. May regulate expression of other M-band proteins via an SRF-dependent pathway. Important for normal contractile function in heart.

Subunit / interactions. Interacts with MYH7 (via C-terminus).

Subcellular location. Cytoplasm. Myofibril. Sarcomere. M line.

Tissue specificity. Highly expressed in skeletal muscle and heart. Not detected in other tissues tested.

Isoforms (2)

UniProt ID	Names	Canonical?
Q96DD0-1	1	yes
Q96DD0-2	2

RefSeq proteins (4): NP_001243314, NP_001243315, NP_001243316, NP_653221* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001611	Leu-rich_rpt	Repeat
IPR003591	Leu-rich_rpt_typical-subtyp	Repeat
IPR032675	LRR_dom_sf	Homologous_superfamily
IPR050216	LRR_domain-containing	Family
IPR055414	LRR_R13L4/SHOC2-like	Domain

Pfam: PF13855, PF23598

UniProt features (13 total): repeat 9, chain 1, coiled-coil region 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96DD0-F1	91.13	0.81

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 69 (showing top): MEF2_02, HUI_MAPK14_TARGETS_UP, IRF1_Q6, chr1p21, HOXA4_Q2, GOCC_M_BAND, MEF2_03, GOCC_A_BAND, TCANNTGAY_SREBP1_01, CHEN_METABOLIC_SYNDROM_NETWORK, WAKABAYASHI_ADIPOGENESIS_PPARG_RXRA_BOUND_8D, YANG_BCL3_TARGETS_UP, GOCC_SUPRAMOLECULAR_COMPLEX, GOCC_SUPRAMOLECULAR_POLYMER, MEF2D_TARGET_GENES

GO Biological Process (1): intracellular signal transduction (GO:0035556)

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

GO Cellular Component (2): M band (GO:0031430), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular anatomical structure	2
cellular anatomical structure	2
signal transduction	1
binding	1
A band	1

Protein interactions and networks

STRING

1186 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LRRC39	RTCA	O00442	609
LRRC39	TRMT13	Q9NUP7	601
LRRC39	DBT	P11182	578
LRRC39	FSD2	A1L4K1	537
LRRC39	DPH5	Q9H2P9	537
LRRC39	MYH7	P12883	531
LRRC39	MBLAC2	Q68D91	499
LRRC39	TERF2IP	Q9NYB0	482
LRRC39	PPP1R42	Q7Z4L9	481
LRRC39	FITM1	A5D6W6	471
LRRC39	FAM219A	Q8IW50	470
LRRC39	ZNF511	Q8NB15	448
LRRC39	TTN	Q8WZ42	442
LRRC39	DRC11L	A6NCM1	429
LRRC39	MYOM3	Q5VTT5	427

IntAct

11 interactions, top by confidence:

A	B	Type	Score
LRRC39	MYH7	psi-mi:“MI:0915”(physical association)	0.510
LRRC39		psi-mi:“MI:0915”(physical association)	0.400
LRRC39	MYH1	psi-mi:“MI:0915”(physical association)	0.370
LRRC39	MYH2	psi-mi:“MI:0915”(physical association)	0.370
LRRC39	MYH6	psi-mi:“MI:0915”(physical association)	0.370
LRRC39	CETN2	psi-mi:“MI:0914”(association)	0.350

BioGRID (29): GSN (Affinity Capture-MS), NINL (Affinity Capture-MS), LIMA1 (Affinity Capture-MS), CETN2 (Affinity Capture-MS), MIPOL1 (Affinity Capture-MS), SUGT1 (Affinity Capture-MS), CNNM4 (Affinity Capture-MS), RAD50 (Affinity Capture-MS), PTP4A1 (Affinity Capture-MS), MYO5B (Affinity Capture-MS), NINL (Affinity Capture-MS), MIPOL1 (Affinity Capture-MS), SUGT1 (Affinity Capture-MS), CETN2 (Affinity Capture-MS), RAD50 (Affinity Capture-MS)

ESM2 similar proteins: A4D1F6, A4IIK1, A6H6A4, A6NIV6, A6NM36, C0STK7, D3ZXS4, F1R6I3, F6R2G2, P14605, Q09562, Q32KX5, Q38SD2, Q3TX51, Q3UHC2, Q3UV48, Q3ZC49, Q4R6F0, Q54AX5, Q58A48, Q5G5E0, Q62192, Q65YW8, Q65Z91, Q66HD6, Q6AXL3, Q6GLE8, Q6GM71, Q6R5N8, Q6ZNQ3, Q7Z2Q7, Q86X40, Q8BGI7, Q8C0R9, Q8N456, Q8VDB8, Q96DD0, Q99467, Q99MB1, Q9BYS8

Diamond homologs: D3ZXS4, F1R6I3, Q3ZC49, Q8BGI7, Q96DD0, Q8VDB8, Q9BYS8

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	56
Likely benign	3
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1339 predictions. Top by Δscore:

Variant	Effect	Δscore
1:100152373:CAAAT:C	donor_gain	1.0000
1:100152377:T:C	donor_gain	1.0000
1:100152380:TATA:T	donor_loss	1.0000
1:100152383:A:C	donor_loss	1.0000
1:100152384:CCTG:C	donor_gain	1.0000
1:100152387:G:A	donor_gain	1.0000
1:100152520:CAAAC:C	acceptor_gain	1.0000
1:100152523:ACCTA:A	acceptor_loss	1.0000
1:100152525:C:CA	acceptor_loss	1.0000
1:100155040:CAA:C	donor_gain	1.0000
1:100156166:TTTTA:T	donor_loss	1.0000
1:100156167:TTTA:T	donor_loss	1.0000
1:100156168:TTAC:T	donor_loss	1.0000
1:100156169:TA:T	donor_loss	1.0000
1:100156170:A:AT	donor_loss	1.0000
1:100156171:CCTT:C	donor_loss	1.0000
1:100156171:CCTTT:C	donor_gain	1.0000
1:100156313:CTGAG:C	acceptor_gain	1.0000
1:100156314:TGAG:T	acceptor_gain	1.0000
1:100156316:AGC:A	acceptor_loss	1.0000
1:100156317:GCTGA:G	acceptor_loss	1.0000
1:100156318:C:CA	acceptor_loss	1.0000
1:100156318:C:CC	acceptor_gain	1.0000
1:100158226:CTAA:C	donor_loss	1.0000
1:100158227:TAACC:T	donor_loss	1.0000
1:100158228:AACC:A	donor_loss	1.0000
1:100158230:CCT:C	donor_gain	1.0000
1:100158230:CCTCT:C	donor_loss	1.0000
1:100158301:AGTT:A	donor_gain	1.0000
1:100158367:CCT:C	acceptor_loss	1.0000

AlphaMissense

2206 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:100158343:A:G	L134P	0.998
1:100159373:A:G	W88R	0.998
1:100159373:A:T	W88R	0.998
1:100156289:A:G	L181P	0.997
1:100158274:A:G	L157P	0.997
1:100156283:A:G	L183P	0.996
1:100158258:G:C	N162K	0.996
1:100158258:G:T	N162K	0.996
1:100158268:A:G	L159P	0.996
1:100152521:A:C	F272L	0.995
1:100152521:A:T	F272L	0.995
1:100152523:A:G	F272L	0.995
1:100156220:A:G	L204P	0.995
1:100156273:G:C	N186K	0.995
1:100156273:G:T	N186K	0.995
1:100158313:A:T	V144D	0.995
1:100159291:C:G	R115P	0.995
1:100155177:A:G	L229P	0.994
1:100158333:G:C	S137R	0.994
1:100158333:G:T	S137R	0.994
1:100158335:T:G	S137R	0.994
1:100160491:A:G	L65S	0.994
1:100156224:A:G	W203R	0.993
1:100156224:A:T	W203R	0.993
1:100158268:A:C	L159R	0.993
1:100158337:A:G	L136P	0.993
1:100159287:G:C	N116K	0.993
1:100159287:G:T	N116K	0.993
1:100152519:A:T	V273D	0.992
1:100155181:A:G	W228R	0.992

dbSNP variants (sampled 300 via entrez): RS1000010624 (1:100156749 G>A), RS1000020668 (1:100161281 A>G), RS1000091392 (1:100150171 A>G), RS1000112530 (1:100168244 A>C), RS1000248172 (1:100164866 C>T), RS1000248585 (1:100153681 A>AT), RS1000322474 (1:100171810 A>G), RS1000374706 (1:100172144 T>C), RS1000458333 (1:100160829 T>G), RS1000523331 (1:100149219 T>C), RS1000531004 (1:100163098 A>G), RS1000595138 (1:100164496 G>A,T), RS1000680226 (1:100181656 G>T), RS1000937121 (1:100177783 C>G,T), RS1001059189 (1:100176132 A>T)

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
GCST009195_7	Temporal pole volume	7.000000e-07

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

16 total (human), top 16 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
lasiocarpine	decreases expression	1
sodium arsenite	decreases expression	1
coumarin	increases phosphorylation	1
pentanal	decreases expression	1
abrine	decreases expression	1
jinfukang	decreases expression	1
incobotulinumtoxinA	decreases expression	1
(+)-JQ1 compound	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Aflatoxin B1	increases methylation	1
Okadaic Acid	decreases expression	1
Acrylamide	increases expression	1
S-Nitrosoglutathione	decreases expression	1
Particulate Matter	increases expression	1

Clinical trials (associated diseases)

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