LRRC74A

Summary

LRRC74A (leucine rich repeat containing 74A, HGNC:23346) is a protein-coding gene on chromosome 14q24.3, encoding Leucine-rich repeat-containing protein 74A (Q0VAA2).

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 84 total
• MANE Select transcript: NM_001385106

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23346
Approved symbol	LRRC74A
Name	leucine rich repeat containing 74A
Location	14q24.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000100565
Ensembl biotype	protein_coding
Entrez	145497

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 4 protein_coding, 3 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

ENST00000216450, ENST00000393774, ENST00000460005, ENST00000484640, ENST00000555189, ENST00000557453, ENST00000689127, ENST00000691122, ENST00000691684

RefSeq mRNA: 4 — MANE Select: NM_001385106 NM_001385106, NM_001385107, NM_001385108, NM_194287

CCDS: CCDS91911, CCDS91912, CCDS9853

Canonical transcript exons

ENST00000689127 — 14 exons

Exon	Start	End
ENSE00003482641	76867356	76867438
ENSE00003483324	76852365	76852450
ENSE00003497668	76865968	76866075
ENSE00003515750	76837875	76837971
ENSE00003524636	76836207	76836314
ENSE00003531053	76844820	76844901
ENSE00003534948	76844423	76844472
ENSE00003623116	76831203	76831375
ENSE00003637740	76853216	76853410
ENSE00003651236	76857380	76857475
ENSE00003664781	76860693	76860839
ENSE00003678432	76828291	76828419
ENSE00003933798	76870125	76870304
ENSE00003936963	76826408	76826734

Expression profiles

Bgee: expression breadth broad, 70 present calls, max score 88.21.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0216 / max 15.3369, expressed in 8 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
140739	0.0145	8
140738	0.0071	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
nasal cavity epithelium	UBERON:0005384	88.21	gold quality
parotid gland	UBERON:0001831	86.70	gold quality
kidney epithelium	UBERON:0004819	85.40	gold quality
left testis	UBERON:0004533	82.85	gold quality
right testis	UBERON:0004534	82.82	gold quality
testis	UBERON:0000473	80.19	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	80.15	gold quality
upper arm skin	UBERON:0004263	79.94	gold quality
vastus lateralis	UBERON:0001379	78.93	gold quality
tendon of biceps brachii	UBERON:0008188	78.68	gold quality
sperm	CL:0000019	78.60	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	78.47	gold quality
quadriceps femoris	UBERON:0001377	77.60	gold quality
myocardium	UBERON:0002349	77.45	gold quality
epithelial cell of pancreas	CL:0000083	77.10	gold quality
biceps brachii	UBERON:0001507	75.90	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	74.99	gold quality
decidua	UBERON:0002450	73.99	gold quality
vena cava	UBERON:0004087	73.36	gold quality
left ventricle myocardium	UBERON:0006566	73.08	gold quality
lateral nuclear group of thalamus	UBERON:0002736	72.90	gold quality
cardiac muscle of right atrium	UBERON:0003379	72.67	gold quality
cartilage tissue	UBERON:0002418	72.63	gold quality
layer of synovial tissue	UBERON:0007616	72.28	gold quality
postcentral gyrus	UBERON:0002581	71.43	gold quality
parietal lobe	UBERON:0001872	71.08	gold quality
thymus	UBERON:0002370	71.04	gold quality
mammalian vulva	UBERON:0000997	70.79	gold quality
secondary oocyte	CL:0000655	70.71	silver quality
entorhinal cortex	UBERON:0002728	70.68	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.75

Regulation

Is transcription factor: no

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	lrrc74a	ENSDARG00000060062
mus_musculus	Lrrc74a	ENSMUSG00000059114
rattus_norvegicus	Lrrc74a	ENSRNOG00000052456

Paralogs (1): LRRC74B (ENSG00000187905)

Protein

Protein identifiers

Leucine-rich repeat-containing protein 74A — Q0VAA2 (reviewed: Q0VAA2)

Alternative names: Leucine-rich repeat-containing protein 74

All UniProt accessions (7): Q0VAA2, A0A8I5KUH5, A0A8I5KUN0, A0A8I5KUZ3, A0A8I5KW16, G3V5G9, H7BXD0

UniProt curated annotations — full annotation on UniProt →

Isoforms (2)

UniProt ID	Names	Canonical?
Q0VAA2-1	1	yes
Q0VAA2-2	2

RefSeq proteins (4): NP_001372035, NP_001372036, NP_001372037, NP_919263 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001611	Leu-rich_rpt	Repeat
IPR032675	LRR_dom_sf	Homologous_superfamily
IPR052394	LRR-containing	Family

Pfam: PF13516

UniProt features (12 total): repeat 8, splice variant 3, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q0VAA2-F1	83.45	0.64

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 27 (showing top): RNGTGGGC_UNKNOWN, PAX8_B, chr14q24, ACTWSNACTNY_UNKNOWN, GINESTIER_BREAST_CANCER_ZNF217_AMPLIFIED_DN, PR_Q2, PAX8_01, DESCARTES_FETAL_CEREBELLUM_MICROGLIA, ARID3B_TARGET_GENES, TCF1P_Q6, DR4_Q2, GSE27786_LSK_VS_NEUTROPHIL_DN, GSE27786_LIN_NEG_VS_NEUTROPHIL_DN, GSE27786_CD4_TCELL_VS_ERYTHTROBLAST_DN, GSE27786_CD4_TCELL_VS_NEUTROPHIL_DN

GO Biological Process (0):

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

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	1

Protein interactions and networks

STRING

269 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LRRC74A	FAM161B	Q96MY7	697
LRRC74A	SPATA31D3	P0C874	664
LRRC74A	SPATA31D4	Q6ZUB0	609
LRRC74A	WDR49	Q8IV35	573
LRRC74A	AREL1	O15033	505
LRRC74A	LIN52	Q52LA3	505
LRRC74A	SERPIND1	P05546	478
LRRC74A	FCF1	Q9Y324	478
LRRC74A	VRTN	Q9H8Y1	470
LRRC74A	PTGR2	Q8N8N7	470
LRRC74A	SNAP29	O95721	446
LRRC74A	THAP7	Q9BT49	434
LRRC74A	ZNF74	Q16587	413
LRRC74A	PCDHB6	Q9Y5E3	400
LRRC74A	BIVM	Q86UB2	393

IntAct

5 interactions, top by confidence:

A	B	Type	Score
CD9	ADAM10	psi-mi:“MI:0914”(association)	0.750
	LRRC74A	psi-mi:“MI:0915”(physical association)	0.400
ECT2L	TOMM40	psi-mi:“MI:0914”(association)	0.350
LRRC74A	EPHA4	psi-mi:“MI:0914”(association)	0.350

BioGRID (6): EPHA4 (Affinity Capture-MS), SMG8 (Affinity Capture-MS), LRRC74A (Affinity Capture-MS), LRRC74A (Cross-Linking-MS (XL-MS)), LRRC74A (Cross-Linking-MS (XL-MS)), ZC3H13 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A0JM56, A0JPI9, A2BFL2, A5PK13, A6H639, J9SQF3, O13066, P19686, P33402, Q02108, Q0VAA2, Q14BP6, Q15111, Q15813, Q3USB7, Q498T9, Q4R642, Q4V8D9, Q4ZHS0, Q5DU41, Q5FVQ9, Q5RAG3, Q5RBD9, Q5RJH2, Q5ZIJ9, Q5ZIU8, Q62688, Q68F79, Q6DN12, Q6GQN5, Q6NU09, Q6P9F7, Q6WRX3, Q7Z7L7, Q80ZJ6, Q8BG40, Q8CDU4, Q8CIR4, Q8CIV8, Q8HXA6

Diamond homologs: A0JPI9, Q0VAA2, Q14BP6, Q6ZQY2, Q86W25, Q95VZ3, A1Z198, A6QLE5, B0FPE9, D4A523, D9I2F9, D9I2G1, D9I2G3, D9I2G4, D9I2H0, E9Q5R7, P10775, P13489, P29315, P59045, P59046, P59047, Q288C4, Q2LKU9, Q3TKR3, Q647I9, Q66X01, Q66X03, Q66X05, Q66X19, Q66X22, Q6B966, Q7RTR0, Q86W24, Q86W28, Q8BU40, Q8HZP9, Q8R4B8, Q8WX94, Q91VI7

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	68
Likely benign	7
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

2826 predictions. Top by Δscore:

Variant	Effect	Δscore
14:76836193:T:A	acceptor_gain	1.0000
14:76836195:T:TA	acceptor_gain	1.0000
14:76836198:T:A	acceptor_gain	1.0000
14:76836202:T:A	acceptor_gain	1.0000
14:76836311:GATG:G	donor_gain	1.0000
14:76853211:T:A	acceptor_gain	1.0000
14:76853212:G:A	acceptor_gain	1.0000
14:76860685:T:TA	acceptor_gain	1.0000
14:76860689:ACAGA:A	acceptor_loss	1.0000
14:76860690:C:G	acceptor_gain	1.0000
14:76860690:CA:C	acceptor_loss	1.0000
14:76860691:A:AC	acceptor_loss	1.0000
14:76860691:A:AG	acceptor_gain	1.0000
14:76860692:G:GA	acceptor_gain	1.0000
14:76860692:GA:G	acceptor_gain	1.0000
14:76860692:GAAC:G	acceptor_gain	1.0000
14:76860836:CCAG:C	donor_loss	1.0000
14:76860837:CAGGT:C	donor_loss	1.0000
14:76860838:AGGTG:A	donor_loss	1.0000
14:76860840:GT:G	donor_loss	1.0000
14:76860841:T:A	donor_loss	1.0000
14:76831201:A:AG	acceptor_gain	0.9900
14:76831202:G:GG	acceptor_gain	0.9900
14:76831202:GAT:G	acceptor_gain	0.9900
14:76831344:GGG:G	donor_gain	0.9900
14:76831345:GGG:G	donor_gain	0.9900
14:76831355:GC:G	donor_gain	0.9900
14:76836199:G:A	acceptor_gain	0.9900
14:76836205:A:AG	acceptor_gain	0.9900
14:76836206:G:GG	acceptor_gain	0.9900

AlphaMissense

3150 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:76831361:G:C	A126P	0.987
14:76831250:G:C	A89P	0.986
14:76831362:C:A	A126D	0.984
14:76852405:T:A	N256K	0.984
14:76852405:T:G	N256K	0.984
14:76852389:T:C	L251P	0.983
14:76852395:T:C	L253P	0.983
14:76836229:T:C	L138P	0.980
14:76844858:C:A	N228K	0.979
14:76844858:C:G	N228K	0.979
14:76831254:G:A	C90Y	0.978
14:76831255:C:G	C90W	0.977
14:76836245:T:A	N143K	0.976
14:76836245:T:G	N143K	0.976
14:76853238:T:C	L279P	0.976
14:76836235:T:C	L140P	0.975
14:76844863:T:C	F230S	0.974
14:76831371:T:C	L129P	0.973
14:76857465:T:C	L365P	0.973
14:76831241:T:G	Y86D	0.971
14:76831320:T:C	L112P	0.971
14:76831356:C:A	A124D	0.971
14:76836274:T:C	L153P	0.971
14:76837889:T:A	N171K	0.971
14:76837889:T:G	N171K	0.971
14:76857391:T:A	N340K	0.971
14:76857391:T:G	N340K	0.971
14:76831253:T:C	C90R	0.967
14:76853406:T:C	L335P	0.967
14:76857465:T:A	L365H	0.966

dbSNP variants (sampled 300 via entrez): RS1000060080 (14:76844035 G>A), RS1000129031 (14:76832303 A>G), RS1000152917 (14:76827752 AG>A), RS1000212016 (14:76840784 C>A,T), RS1000334490 (14:76835498 A>G), RS1000388155 (14:76835196 A>G), RS1000461206 (14:76868713 G>A,C), RS1000512969 (14:76868470 A>G), RS1000563999 (14:76840890 G>A), RS1000567280 (14:76827408 A>G), RS1000623394 (14:76828596 G>A,T), RS1000853401 (14:76859621 G>C), RS1000911829 (14:76857223 C>A,G,T), RS1000961938 (14:76856952 T>C), RS1001199921 (14:76825785 G>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

5 associations (top):

Study	Trait	p-value
GCST004274_4	Venlafaxine response in generalised anxiety disorder (remitters vs non-remitters after 12 weeks)	9.000000e-06
GCST005352_11	Paclitaxel disposition in epithelial ovarian cancer	2.000000e-06
GCST006061_118	Atrial fibrillation	1.000000e-10
GCST006061_193	Atrial fibrillation	2.000000e-09
GCST010118_98	Type 2 diabetes	8.000000e-11

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

12 total (human), top 12 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
propionaldehyde	increases methylation	1
nonanal	increases methylation	1
n-hexanal	increases methylation	1
butyraldehyde	increases methylation	1
caprylic aldehyde	increases methylation	1
pentanal	increases methylation	1
heptanal	increases methylation	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Cadmium	decreases expression, increases abundance	1
Estradiol	affects binding, increases expression	1
Aflatoxin B1	increases methylation	1
Cadmium Chloride	increases abundance, decreases expression	1

Clinical trials (associated diseases)

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