LRRC37B

Summary

LRRC37B (leucine rich repeat containing 37B, HGNC:29070) is a protein-coding gene on chromosome 17q11.2, encoding Leucine-rich repeat-containing protein 37B (Q96QE4). It is a selective cancer dependency (DepMap: 37.3% of cell lines).

Predicted to be located in membrane.

Source: NCBI Gene 114659 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 173 total — 1 pathogenic
• Cancer dependency (DepMap): dependent in 37.3% of screened cell lines
• MANE Select transcript: NM_001321350

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29070
Approved symbol	LRRC37B
Name	leucine rich repeat containing 37B
Location	17q11.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000185158
Ensembl biotype	protein_coding
OMIM	616558
Entrez	114659

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 11 protein_coding, 8 retained_intron, 3 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000341671, ENST00000543378, ENST00000578118, ENST00000578674, ENST00000579094, ENST00000579206, ENST00000579766, ENST00000580303, ENST00000580871, ENST00000581086, ENST00000581370, ENST00000581786, ENST00000582117, ENST00000582815, ENST00000583204, ENST00000583342, ENST00000583758, ENST00000584368, ENST00000902794, ENST00000902795, ENST00000902796, ENST00000935425, ENST00000941835

RefSeq mRNA: 2 — MANE Select: NM_001321350 NM_001321350, NM_052888

CCDS: CCDS32609, CCDS82102

Canonical transcript exons

ENST00000543378 — 15 exons

Exon	Start	End
ENSE00001519331	32053266	32053487
ENSE00002211306	32021393	32022825
ENSE00002241663	32020697	32020803
ENSE00002265414	32017972	32018054
ENSE00002691909	32007383	32008132
ENSE00003458238	32031378	32031458
ENSE00003524379	32035565	32035639
ENSE00003565252	32050003	32050107
ENSE00003579070	32047761	32047901
ENSE00003608220	32045700	32045818
ENSE00003609203	32030656	32030727
ENSE00003629511	32024711	32024782
ENSE00003660995	32049102	32049394
ENSE00003669785	32027769	32027840
ENSE00003691372	32034910	32034981

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 96.23.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.1040 / max 123.6226, expressed in 1717 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
160218	8.0438	1717
160219	0.0602	10

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cerebellar cortex	UBERON:0002129	96.23	gold quality
cerebellar hemisphere	UBERON:0002245	96.22	gold quality
cerebellum	UBERON:0002037	96.18	gold quality
ventricular zone	UBERON:0003053	96.10	gold quality
right hemisphere of cerebellum	UBERON:0014890	95.94	gold quality
cortical plate	UBERON:0005343	95.81	gold quality
ganglionic eminence	UBERON:0004023	93.98	gold quality
corpus callosum	UBERON:0002336	93.75	gold quality
left testis	UBERON:0004533	92.10	gold quality
right testis	UBERON:0004534	92.07	gold quality
primary visual cortex	UBERON:0002436	91.73	gold quality
pituitary gland	UBERON:0000007	91.40	gold quality
testis	UBERON:0000473	91.34	gold quality
Ammon’s horn	UBERON:0001954	91.26	gold quality
sural nerve	UBERON:0015488	91.06	gold quality
brain	UBERON:0000955	90.88	gold quality
amygdala	UBERON:0001876	90.84	gold quality
nucleus accumbens	UBERON:0001882	90.84	gold quality
right uterine tube	UBERON:0001302	90.80	gold quality
left ovary	UBERON:0002119	90.76	gold quality
temporal lobe	UBERON:0001871	90.75	gold quality
right frontal lobe	UBERON:0002810	90.72	gold quality
superior frontal gyrus	UBERON:0002661	90.62	gold quality
caudate nucleus	UBERON:0001873	90.59	gold quality
adenohypophysis	UBERON:0002196	90.54	gold quality
Brodmann (1909) area 9	UBERON:0013540	90.43	gold quality
granulocyte	CL:0000094	90.33	gold quality
putamen	UBERON:0001874	90.33	gold quality
lower esophagus mucosa	UBERON:0035834	90.31	gold quality
ovary	UBERON:0000992	90.24	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-MTAB-7303	no	179.62
E-MTAB-7381	no	50.11
E-ANND-3	no	4.50

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

30 targeting LRRC37B, 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-4795-3P	100.00	74.62	4024
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488
HSA-MIR-548D-5P	99.94	71.23	3502
HSA-MIR-548H-5P	99.94	71.24	3488
HSA-MIR-548O-5P	99.94	71.24	3488
HSA-MIR-548W	99.94	71.24	3488
HSA-MIR-548Y	99.94	71.28	3514
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-5571-5P	99.49	66.99	1764
HSA-MIR-3973	99.20	69.19	1990
HSA-MIR-6512-5P	98.76	69.29	1195
HSA-MIR-3928-3P	97.61	66.53	1096

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 37.3% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 1)

• LRRC37B is a human modifier of voltage-gated sodium channels and axon excitability in cortical neurons. (PMID:38134874)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Lrrc37	ENSMUSG00000034239
mus_musculus	Lrrc37a	ENSMUSG00000078632
rattus_norvegicus	Lrrc37a	ENSRNOG00000042025
rattus_norvegicus	Prp2l1	ENSRNOG00000042833

Paralogs (3): LRRC37A (ENSG00000176681), LRRC37A3 (ENSG00000176809), LRRC37A2 (ENSG00000238083)

Protein

Protein identifiers

Leucine-rich repeat-containing protein 37B — Q96QE4 (reviewed: Q96QE4)

Alternative names: C66 SLIT-like testicular protein

All UniProt accessions (7): Q96QE4, F5H5K1, J3KTP0, J3QKM3, J3QL10, J3QLE7, J3QLI7

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Membrane.

Isoforms (2)

UniProt ID	Names	Canonical?
Q96QE4-1	1	yes
Q96QE4-2	2

RefSeq proteins (2): NP_001308279, NP_443120 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001611	Leu-rich_rpt	Repeat
IPR003591	Leu-rich_rpt_typical-subtyp	Repeat
IPR015753	LRRC37	Family
IPR029423	LRRC37AB_C	Domain
IPR032675	LRR_dom_sf	Homologous_superfamily
IPR032754	LRRC37_N	Domain

Pfam: PF13855, PF14914, PF15779

UniProt features (32 total): sequence conflict 9, repeat 6, region of interest 4, compositionally biased region 4, topological domain 2, glycosylation site 2, signal peptide 1, chain 1, coiled-coil region 1, splice variant 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96QE4-F1	53.35	0.18

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Glycosylation sites (2): 358, 789

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 42 (showing top): GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_UP, chr17q11, KOINUMA_TARGETS_OF_SMAD2_OR_SMAD3, ZWANG_DOWN_BY_2ND_EGF_PULSE, CDC5L_TARGET_GENES, TFEB_TARGET_GENES, ZBTB1_TARGET_GENES, ZNF184_TARGET_GENES, ZNF2_TARGET_GENES, ZNF274_TARGET_GENES, ZNF33A_TARGET_GENES, ZNF410_TARGET_GENES, ZSCAN30_TARGET_GENES, MIR548D_3P, MIR548H_3P_MIR548Z

GO Biological Process (0):

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

GO Cellular Component (1): membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

210 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LRRC37B	CRLF3	Q8IUI8	723
LRRC37B	UTP6	Q9NYH9	719
LRRC37B	ADAP2	Q9NPF8	691
LRRC37B	RAB11FIP4	Q86YS3	664
LRRC37B	ATAD5	Q96QE3	650
LRRC37B	TEFM	Q96QE5	624
LRRC37B	COPRS	Q9NQ92	623
LRRC37B	EVI2A	P22794	580
LRRC37B	RNF135	Q8IUD6	571
LRRC37B	EVI2B	P34910	507
LRRC37B	SUZ12	Q15022	479
LRRC37B	NF1	P21359	445
LRRC37B	NPIPB6	E9PJ23	406
LRRC37B	TMEM255B	Q8WV15	380
LRRC37B	OMG	P23515	348

IntAct

4 interactions, top by confidence:

A	B	Type	Score
LRRC37B	CFTR	psi-mi:“MI:0915”(physical association)	0.370
NEK4	E2F8	psi-mi:“MI:0914”(association)	0.350
LRRC37B	HLA-F	psi-mi:“MI:0914”(association)	0.350

BioGRID (7): LRRC37B (Affinity Capture-RNA), LRRC37B (Affinity Capture-MS), HLA-F (Affinity Capture-MS), METAP2 (Affinity Capture-MS), MAN2A2 (Affinity Capture-MS), LRRC37B (PCA), LRRC37B (Affinity Capture-RNA)

ESM2 similar proteins: A0A1B0GUW6, A1EGX6, A6NM11, A6NMS7, A6QLF8, D3YU32, I3L273, J3KML8, O35930, O60309, Q08DY0, Q14242, Q2TBI7, Q32KG4, Q32L62, Q3MIW9, Q3TNW5, Q3V0E1, Q4R729, Q5VWK0, Q5VYM1, Q62170, Q659K0, Q68DN1, Q6AZ54, Q6MG22, Q6UXB8, Q6ZRG5, Q8BUE7, Q8K4E0, Q8N307, Q8N3K9, Q8TCU4, Q8WNU4, Q8WXI7, Q95JY5, Q96F05, Q96JA4, Q96M34, Q96M43

Diamond homologs: A6NM11, A6NMS7, O60309, Q49AS3, Q96QE4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	134
Likely benign	19
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
981056	GRCh37/hg19 17q11.2-12(chr17:29989741-32355632)	Pathogenic

SpliceAI

1548 predictions. Top by Δscore:

Variant	Effect	Δscore
17:32024781:CT:C	donor_gain	1.0000
17:32024783:G:GG	donor_gain	1.0000
17:32027841:G:GG	donor_gain	1.0000
17:32027845:G:GG	donor_gain	1.0000
17:32030728:G:GG	donor_gain	1.0000
17:32031455:ACTT:A	donor_gain	1.0000
17:32031456:CTT:C	donor_gain	1.0000
17:32031459:G:GG	donor_gain	1.0000
17:32034901:A:AG	acceptor_gain	1.0000
17:32034904:TTTCA:T	acceptor_loss	1.0000
17:32034905:TTCAG:T	acceptor_loss	1.0000
17:32034906:TCA:T	acceptor_loss	1.0000
17:32034907:CAG:C	acceptor_loss	1.0000
17:32034908:A:AC	acceptor_loss	1.0000
17:32034908:A:AG	acceptor_gain	1.0000
17:32034909:G:GA	acceptor_gain	1.0000
17:32034909:G:T	acceptor_loss	1.0000
17:32034909:GA:G	acceptor_gain	1.0000
17:32034909:GAA:G	acceptor_gain	1.0000
17:32034909:GAATT:G	acceptor_gain	1.0000
17:32034977:TATCT:T	donor_gain	1.0000
17:32034978:ATCT:A	donor_gain	1.0000
17:32034979:TCT:T	donor_gain	1.0000
17:32034980:CT:C	donor_gain	1.0000
17:32034981:TGTAA:T	donor_loss	1.0000
17:32034982:G:GA	donor_loss	1.0000
17:32034982:G:GG	donor_gain	1.0000
17:32034983:TA:T	donor_loss	1.0000
17:32034984:AAGTA:A	donor_loss	1.0000
17:32035563:A:AG	acceptor_gain	1.0000

AlphaMissense

5635 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:32027784:T:A	N589K	0.982
17:32027784:T:G	N589K	0.982
17:32024754:T:A	W575R	0.981
17:32024754:T:C	W575R	0.981
17:32024756:G:C	W575C	0.980
17:32024756:G:T	W575C	0.980
17:32024782:T:C	L584P	0.980
17:32035639:T:C	L708P	0.980
17:32031393:T:A	N637K	0.977
17:32031393:T:G	N637K	0.977
17:32030671:T:A	N613K	0.973
17:32030671:T:G	N613K	0.973
17:32030670:A:T	N613I	0.970
17:32024726:C:A	N565K	0.966
17:32024726:C:G	N565K	0.966
17:32034925:T:A	N664K	0.964
17:32034925:T:G	N664K	0.964
17:32022743:T:C	C533R	0.963
17:32034981:T:C	L683P	0.963
17:32030699:T:C	F623L	0.962
17:32030701:T:A	F623L	0.962
17:32030701:T:G	F623L	0.962
17:32024716:T:C	F562S	0.961
17:32022743:T:A	C533S	0.960
17:32022744:G:C	C533S	0.960
17:32031421:T:C	F647L	0.960
17:32031423:T:A	F647L	0.960
17:32031423:T:G	F647L	0.960
17:32031392:A:T	N637I	0.953
17:32027774:T:C	L586P	0.952

dbSNP variants (sampled 300 via entrez): RS1000179219 (17:32036266 G>GCTA), RS1000240553 (17:32029013 T>A,G), RS1000292902 (17:32029163 AG>A), RS1000621029 (17:32042299 C>T), RS1000636006 (17:32035967 A>G,T), RS1000678193 (17:32042030 T>A,C), RS1000716461 (17:32011303 A>G), RS1000783298 (17:32049943 TTCTC>T,TTC,TTCTCTC), RS1000791158 (17:32017588 T>G), RS1000843611 (17:32017938 G>A,T), RS1000901414 (17:32049789 C>T), RS1001025312 (17:32023391 G>A), RS1001064507 (17:32011051 C>T), RS1001161316 (17:32046096 A>G), RS1001271955 (17:32053430 G>A)

Disease associations

OMIM: gene MIM:616558 | disease phenotypes: MIM:615972, MIM:618786

GenCC curated gene-disease

Mondo (2): nanophthalmos 4 (MONDO:0014426), Imagawa-Matsumoto syndrome (MONDO:0032916)

Orphanet (2): Nanophthalmos (Orphanet:35612), Imagawa-Matsumoto syndrome (Orphanet:659463)

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST000817_41	Height	3.000000e-08
GCST006151_3	Memory dysfunction in frontotemporal lobe dementia	8.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0001072	memory impairment

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

19 total (human), top 19 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases abundance, increases expression	2
Valproic Acid	affects expression, decreases expression	2
aristolochic acid I	increases expression	1
beta-lapachone	increases expression	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
abrine	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Arsenic	decreases expression, increases abundance	1
Benzo(a)pyrene	affects methylation	1
Cisplatin	increases expression	1
Doxorubicin	decreases expression	1
Gallic Acid	increases expression	1
Hydrogen Peroxide	affects expression	1
Tobacco Smoke Pollution	decreases expression	1
Aflatoxin B1	increases expression	1
Copper Sulfate	decreases expression	1
Lactic Acid	decreases expression	1
Particulate Matter	increases abundance, increases expression	1

Clinical trials (associated diseases)

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