LRRC74B

Summary

LRRC74B (leucine rich repeat containing 74B, HGNC:34301) is a protein-coding gene on chromosome 22q11.21, encoding Leucine-rich repeat-containing protein 74B (Q6ZQY2).

At a glance

• Clinical variants (ClinVar): 9 total — 1 pathogenic
• MANE Select transcript: NM_001291006

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:34301
Approved symbol	LRRC74B
Name	leucine rich repeat containing 74B
Location	22q11.21
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000187905
Ensembl biotype	protein_coding
Entrez	400891

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 3 retained_intron, 1 protein_coding

ENST00000442047, ENST00000469766, ENST00000473769, ENST00000497328

RefSeq mRNA: 1 — MANE Select: NM_001291006 NM_001291006

CCDS: CCDS77654

Canonical transcript exons

ENST00000442047 — 10 exons

Exon	Start	End
ENSE00001493908	21045946	21046125
ENSE00001656293	21047884	21048016
ENSE00001675618	21057105	21057200
ENSE00001684710	21060373	21060577
ENSE00001777107	21048951	21049157
ENSE00003537485	21047356	21047498
ENSE00003550910	21053360	21053475
ENSE00003665361	21052249	21052358
ENSE00003666167	21055098	21055176
ENSE00003968734	21061724	21064168

Expression profiles

Bgee: expression breadth broad, 87 present calls, max score 97.63.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1547 / max 18.1714, expressed in 84 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
191182	0.1547	84

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	97.63	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	88.52	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.18	gold quality
left testis	UBERON:0004533	77.68	gold quality
right testis	UBERON:0004534	77.44	gold quality
testis	UBERON:0000473	73.91	gold quality
right lung	UBERON:0002167	71.82	gold quality
left uterine tube	UBERON:0001303	67.20	gold quality
right hemisphere of cerebellum	UBERON:0014890	64.57	gold quality
cerebellar hemisphere	UBERON:0002245	64.49	gold quality
cerebellar cortex	UBERON:0002129	64.32	gold quality
nasal cavity mucosa	UBERON:0001826	63.72	gold quality
cerebellum	UBERON:0002037	62.60	gold quality
fallopian tube	UBERON:0003889	62.29	gold quality
pituitary gland	UBERON:0000007	58.26	gold quality
lower esophagus mucosa	UBERON:0035834	58.08	gold quality
adenohypophysis	UBERON:0002196	57.84	gold quality
caudate nucleus	UBERON:0001873	55.67	gold quality
hypothalamus	UBERON:0001898	54.61	gold quality
upper lobe of left lung	UBERON:0008952	53.87	gold quality
sural nerve	UBERON:0015488	53.27	gold quality
upper lobe of lung	UBERON:0008948	52.58	gold quality
stromal cell of endometrium	CL:0002255	52.52	silver quality
endocervix	UBERON:0000458	50.72	gold quality
lung	UBERON:0002048	50.58	gold quality
Ammon’s horn	UBERON:0001954	49.67	gold quality
amygdala	UBERON:0001876	49.02	gold quality
endometrium	UBERON:0001295	48.79	gold quality
hindlimb stylopod muscle	UBERON:0004252	48.30	gold quality
brain	UBERON:0000955	47.91	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	10.48

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

77 targeting LRRC74B, 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-126-5P	100.00	72.71	3180
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-2052	99.79	69.37	2031
HSA-MIR-26A-5P	99.78	73.52	2303
HSA-MIR-26B-5P	99.78	73.51	2305
HSA-MIR-3934-3P	99.76	65.51	1351
HSA-MIR-4524A-3P	99.72	66.85	2406
HSA-MIR-4465	99.71	72.56	2096
HSA-MIR-1284	99.67	73.56	1353
HSA-MIR-4328	99.57	71.06	4094
HSA-MIR-12123	99.52	71.79	2990
HSA-MIR-4437	99.52	65.29	1266
HSA-MIR-409-3P	99.50	66.33	1192
HSA-MIR-19A-5P	99.36	66.93	1675
HSA-MIR-19B-1-5P	99.36	67.07	1669
HSA-MIR-19B-2-5P	99.36	67.07	1669
HSA-MIR-4796-5P	99.34	70.06	810
HSA-MIR-4506	99.34	67.47	526
HSA-MIR-504-3P	99.30	67.18	1745

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	lrrc74b	ENSDARG00000098365
mus_musculus	Lrrc74b	ENSMUSG00000022759
rattus_norvegicus	Lrrc74b	ENSRNOG00000001872

Paralogs (1): LRRC74A (ENSG00000100565)

Protein

Protein identifiers

Leucine-rich repeat-containing protein 74B — Q6ZQY2 (reviewed: Q6ZQY2)

All UniProt accessions (1): Q6ZQY2

Isoforms (2)

UniProt ID	Names	Canonical?
Q6ZQY2-1	1	yes
Q6ZQY2-2	2

RefSeq proteins (1): NP_001277935* (*=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 (14 total): repeat 9, sequence variant 2, chain 1, region of interest 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6ZQY2-F1	84.30	0.73

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 31 (showing top): MIKKELSEN_ES_ICP_WITH_H3K4ME3, ASH1L_TARGET_GENES, CEBPZ_TARGET_GENES, CHAF1B_TARGET_GENES, FOXJ2_TARGET_GENES, PRKDC_TARGET_GENES, SUPT16H_TARGET_GENES, MIR4795_3P, MIR1297, MIR126_5P, MIR6844, MIR6778_3P, MIR619_5P, MIR504_3P, MIR6509_3P

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

231 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LRRC74B	CCT8L2	Q96SF2	571
LRRC74B	GAB4	Q2WGN9	548
LRRC74B	RIMBP3C	A6NJZ7	548
LRRC74B	FAM47E	Q6ZV65	530
LRRC74B	LMNTD1	Q8N9Z9	528
LRRC74B	LRRC18	Q8N456	517
LRRC74B	ATP6AP1L	Q52LC2	514
LRRC74B	AUNIP	Q9H7T9	479
LRRC74B	HNRNPA1L2	Q32P51	471
LRRC74B	THAP7	Q9BT49	447
LRRC74B	DTHD1	Q6ZMT9	436
LRRC74B	ZNF74	Q16587	432
LRRC74B	LZTR1	Q8N653	426
LRRC74B	CCDC62	Q6P9F0	400
LRRC74B	PI4KA	P42356	400

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: A5PJJ5, A6NHZ5, E9Q5R7, G1T469, G3XA59, P02750, P10775, P13489, P22792, P29315, P59046, P59047, Q14392, Q149C3, Q14BP6, Q15048, Q32PG9, Q3UJB3, Q3V3V9, Q3ZBI5, Q53B87, Q53B88, Q569B5, Q5BK65, Q5DU56, Q5RF01, Q63035, Q640Z9, Q647I9, Q6F5E8, Q6QMY6, Q6UY01, Q6UY18, Q6ZQY2, Q7RTR2, Q86W24, Q86W25, Q86YC3, Q8BMT4, Q8CBR6

Diamond homologs: A0JPI9, Q0VAA2, Q14BP6, Q6ZQY2, Q86W25, Q95VZ3

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
2579266	GRCh38/hg38 22q11.21(chr22:18985739-21081116)x1	Pathogenic

SpliceAI

1848 predictions. Top by Δscore:

Variant	Effect	Δscore
22:21046122:G:GT	donor_gain	1.0000
22:21046123:A:T	donor_gain	1.0000
22:21049154:GCAG:G	donor_gain	1.0000
22:21049155:C:T	donor_gain	1.0000
22:21055174:GTA:G	donor_gain	1.0000
22:21055177:G:GG	donor_gain	1.0000
22:21046122:G:T	donor_gain	0.9900
22:21048949:A:AG	acceptor_gain	0.9900
22:21048950:G:GG	acceptor_gain	0.9900
22:21048950:GAT:G	acceptor_gain	0.9900
22:21049155:CAGG:C	donor_loss	0.9900
22:21049156:AG:A	donor_loss	0.9900
22:21049157:GGTA:G	donor_loss	0.9900
22:21049158:G:GC	donor_loss	0.9900
22:21049159:T:A	donor_loss	0.9900
22:21053473:GAGGT:G	donor_loss	0.9900
22:21053474:AGG:A	donor_loss	0.9900
22:21053475:GGTGA:G	donor_loss	0.9900
22:21053476:GT:G	donor_loss	0.9900
22:21053477:T:A	donor_loss	0.9900
22:21055096:A:AG	acceptor_gain	0.9900
22:21055097:G:GA	acceptor_gain	0.9900
22:21055097:GT:G	acceptor_gain	0.9900
22:21055097:GTAAC:G	acceptor_gain	0.9900
22:21055172:TTGTA:T	donor_gain	0.9900
22:21057201:G:GG	donor_gain	0.9900
22:21046088:TCCCG:T	donor_gain	0.9800
22:21046122:GAAGG:G	donor_loss	0.9800
22:21046123:AAG:A	donor_loss	0.9800
22:21046124:AG:A	donor_loss	0.9800

AlphaMissense

2517 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:21052313:T:A	N229K	0.972
22:21052313:T:G	N229K	0.972
22:21057116:T:A	N313K	0.972
22:21057116:T:G	N313K	0.972
22:21053466:T:C	L280P	0.969
22:21053398:T:A	N257K	0.962
22:21053398:T:G	N257K	0.962
22:21055104:C:A	N285K	0.962
22:21055104:C:G	N285K	0.962
22:21052297:T:C	L224P	0.961
22:21055109:T:C	I287T	0.957
22:21053466:T:A	L280H	0.954
22:21053457:T:C	L277S	0.949
22:21053365:C:A	N246K	0.948
22:21053365:C:G	N246K	0.948
22:21053373:T:A	L249H	0.947
22:21057114:A:G	N313D	0.945
22:21052309:G:T	W228L	0.937
22:21053439:T:C	L271P	0.936
22:21053435:G:C	A270P	0.933
22:21052297:T:A	L224H	0.931
22:21053382:T:C	L252P	0.929
22:21049128:T:C	L198P	0.928
22:21052308:T:A	W228R	0.927
22:21052308:T:C	W228R	0.927
22:21053466:T:G	L280R	0.924
22:21048970:C:A	N145K	0.923
22:21048970:C:G	N145K	0.923
22:21052345:C:A	A240D	0.923
22:21052280:C:A	N218K	0.921

dbSNP variants (sampled 300 via entrez): RS1000068049 (22:21050187 C>A,T), RS1000119798 (22:21049882 T>C), RS1000303593 (22:21045045 CAT>C), RS1000359506 (22:21055140 G>A), RS1000419704 (22:21054158 T>A,C), RS1000568949 (22:21045344 G>A,C), RS1000594258 (22:21063658 C>A,T), RS1000700386 (22:21052668 C>T), RS1000769452 (22:21053918 C>G,T), RS1001016582 (22:21061144 A>G), RS1001390032 (22:21062086 T>C), RS1001528930 (22:21056449 C>T), RS1001560199 (22:21056798 G>A), RS1001563842 (22:21053223 C>T), RS1001801074 (22:21051105 T>C)

Disease associations

OMIM: gene `` | disease phenotypes: MIM:188400

GenCC curated gene-disease

Mondo (1): DiGeorge syndrome (MONDO:0008564)

Orphanet (1): 22q11.2 deletion syndrome (Orphanet:567)

HPO phenotypes

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

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D004062	DiGeorge Syndrome	C05.660.207.103.500; C14.240.400.021.500; C14.280.400.044.500; C15.604.451.249.500; C16.131.077.019.500; C16.131.240.400.021.500; C16.131.260.019.500; C16.131.482.249.500; C16.131.621.207.103.500; C16.320.180.019.500; C19.642.482.500.500

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

9 total (human), top 9 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, affects response to substance, increases expression	1
clothianidin	decreases expression	1
Acetaminophen	increases expression	1
Benzo(a)pyrene	increases methylation	1
Lipopolysaccharides	affects cotreatment, affects response to substance, increases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	increases methylation	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00395538	PHASE3	TERMINATED	Effects of PTH Replacement on Bone in Hypoparathyroidism
NCT00576407	PHASE2	COMPLETED	Thymus Transplantation in DiGeorge Syndrome #668
NCT00576836	PHASE2	COMPLETED	Thymus Transplantation Dose in DiGeorge #932
NCT01821781	PHASE2	ACTIVE_NOT_RECRUITING	Immune Disorder HSCT Protocol
NCT05149898	PHASE2	COMPLETED	Open-Label Study of ZYN002 Administered as a Transdermal Gel to Children and Adolescents With 22q11.2 Deletion Syndrome (INSPIRE)
NCT07284641	PHASE2	RECRUITING	Hematopoietic Stem Cell Transplantation (HSCT) for Common Variable Immunodeficiency (CVID) and Other Autoimmune Manifestations of Primary Immune Regulatory Disorders (PIRD)
NCT00566488	PHASE1	COMPLETED	Parathyroid and Thymus Transplantation in DiGeorge #931
NCT00579709	PHASE1	COMPLETED	Thymus Transplantation With Immunosuppression
NCT00849888	PHASE1	TERMINATED	Serum-Free Thymus Transplantation in DiGeorge Anomaly
NCT02895906	PHASE1	COMPLETED	Safety and Efficacy Study of NFC-1 in Subjects Aged 12-17 Years With 22q11.2DS & Associated Neuropsychiatric Conditions
NCT00579527	PHASE1/PHASE2	COMPLETED	Phase I/II Thymus Transplantation With Immunosuppression #950
NCT00004351	Not specified	COMPLETED	Study of Phenotype and Genotype Correlations in Patients With Contiguous Gene Deletion Syndromes
NCT00005102	Not specified	UNKNOWN	Immunologic Evaluation in Patients With DiGeorge Syndrome or Velocardiofacial Syndrome
NCT00105274	Not specified	COMPLETED	Velocardiofacial (VCFS; 22q11.2; DiGeorge) Syndrome Study
NCT00278005	Not specified	TERMINATED	Infection in DiGeorge Following CHD Surgery
NCT00556530	Not specified	RECRUITING	Examining Genetic Factors That Affect the Severity of 22q11.2 Deletion Syndrome
NCT00916955	Not specified	COMPLETED	Genetic Modifiers for 22q11.2 Syndrome
NCT01220531	Not specified	COMPLETED	Thymus Transplantation Safety-Efficacy
NCT01781923	Not specified	COMPLETED	Cognitive Remediation in 22q11DS
NCT02381457	Not specified	COMPLETED	SNP-based Microdeletion and Aneuploidy RegisTry (SMART)
NCT02430584	Not specified	UNKNOWN	Whole Blood Specimen Collection From Pregnant Subjects
NCT02460328	Not specified	COMPLETED	Resolution of Primary Immune Defect in 22q11.2 Deletion Syndrome
NCT02787486	Not specified	COMPLETED	Expanded Noninvasive Genomic Medical Assessment: The Enigma Study
NCT03284060	Not specified	TERMINATED	Social Cognition Training and Cognitive Remediation
NCT04141540	Not specified	COMPLETED	Molecular Variants Associated With Schizophrenia: Differential Analysis of Monozygotic Twins With Variable Phenotypic 22q11
NCT04373226	Not specified	TERMINATED	Arithmetic Abilities in Children With 22q11.2DS
NCT04639388	Not specified	RECRUITING	Understanding of Psychotic Disorders in Children With 22q11.2DS
NCT04639960	Not specified	TERMINATED	Neuroprotective Effects of Risperdal on Brain and Cognition in 22q11 Deletion Syndrome
NCT04647500	Not specified	COMPLETED	Effects of Methylphenidate on Brain and Cognition in 22q11 Deletion Syndrome
NCT05924347	Not specified	RECRUITING	Early Scoliotic Changes in Children at Increased Risk for Scoliosis Development
NCT07493096	Not specified	RECRUITING	Intensive Multimodal Neurorehabilitation Targeting Neuroplasticity in Pediatric Neurodevelopmental and Chromosomal Disorders