LRRIQ3

Summary

LRRIQ3 (leucine rich repeats and IQ motif containing 3, HGNC:28318) is a protein-coding gene on chromosome 1p31.1, encoding Leucine-rich repeat and IQ domain-containing protein 3 (A6PVS8).

At a glance

• GWAS associations: 18
• Clinical variants (ClinVar): 105 total
• MANE Select transcript: NM_001105659

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28318
Approved symbol	LRRIQ3
Name	leucine rich repeats and IQ motif containing 3
Location	1p31.1
Locus type	gene with protein product
Status	Approved
Aliases	MGC22773
Ensembl gene	ENSG00000162620
Ensembl biotype	protein_coding
OMIM	617957
Entrez	127255

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 6 protein_coding, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000354431, ENST00000370909, ENST00000370911, ENST00000395089, ENST00000415760, ENST00000417067, ENST00000444984, ENST00000463724, ENST00000468759, ENST00000495179

RefSeq mRNA: 2 — MANE Select: NM_001105659 NM_001105659, NM_001322315

CCDS: CCDS41350

Canonical transcript exons

ENST00000354431 — 8 exons

Exon	Start	End
ENSE00003484052	74074661	74074790
ENSE00003491427	74109394	74109553
ENSE00003844175	74183436	74183684
ENSE00003847426	74197996	74198176
ENSE00003888990	74155733	74155866
ENSE00003889728	74182538	74182861
ENSE00003891531	74041213	74041933
ENSE00003894576	74026015	74026969

Expression profiles

Bgee: expression breadth ubiquitous, 165 present calls, max score 85.51.

FANTOM5 (CAGE): breadth broad, TPM avg 1.1960 / max 66.4636, expressed in 634 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
12846	0.8895	517
12844	0.2406	126
12845	0.0659	20

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.51	gold quality
left testis	UBERON:0004533	83.22	gold quality
right testis	UBERON:0004534	82.63	gold quality
testis	UBERON:0000473	82.30	gold quality
buccal mucosa cell	CL:0002336	82.20	silver quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	80.28	gold quality
sperm	CL:0000019	80.03	gold quality
secondary oocyte	CL:0000655	78.88	gold quality
oocyte	CL:0000023	78.60	gold quality
bronchial epithelial cell	CL:0002328	77.43	gold quality
bronchus	UBERON:0002185	75.77	gold quality
adult organism	UBERON:0007023	73.04	gold quality
right uterine tube	UBERON:0001302	69.33	gold quality
mucosa of paranasal sinus	UBERON:0005030	68.90	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	68.01	gold quality
islet of Langerhans	UBERON:0000006	67.52	gold quality
ventricular zone	UBERON:0003053	65.93	gold quality
adrenal tissue	UBERON:0018303	64.93	gold quality
right adrenal gland cortex	UBERON:0035827	64.01	gold quality
right adrenal gland	UBERON:0001233	62.99	gold quality
epithelium of nasopharynx	UBERON:0001951	62.13	silver quality
left adrenal gland	UBERON:0001234	61.01	gold quality
vermiform appendix	UBERON:0001154	60.97	gold quality
lower lobe of lung	UBERON:0008949	60.61	silver quality
adrenal gland	UBERON:0002369	60.36	gold quality
left adrenal gland cortex	UBERON:0035825	60.24	gold quality
stromal cell of endometrium	CL:0002255	59.65	gold quality
adrenal cortex	UBERON:0001235	59.58	gold quality
omental fat pad	UBERON:0010414	59.50	gold quality
peritoneum	UBERON:0002358	59.45	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	4.77

Regulation

Is transcription factor: no

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	lrriq3	ENSDARG00000078611
mus_musculus	Lrriq3	ENSMUSG00000028182
rattus_norvegicus	Lrriq3	ENSRNOG00000009555
drosophila_melanogaster	TbCMF46	FBGN0032163
drosophila_melanogaster	Ppr-Y	FBGN0046697

Paralogs (13): LRRC23 (ENSG00000010626), LRRC61 (ENSG00000127399), DNAAF11 (ENSG00000129295), LRRC9 (ENSG00000131951), LRRCC1 (ENSG00000133739), LRRC49 (ENSG00000137821), LRRC46 (ENSG00000141294), DNAAF1 (ENSG00000154099), LRGUK (ENSG00000155530), LRRC43 (ENSG00000158113), DRC3 (ENSG00000171962), PPP1R42 (ENSG00000178125), CEP97 (ENSG00000182504)

Protein

Protein identifiers

Leucine-rich repeat and IQ domain-containing protein 3 — A6PVS8 (reviewed: A6PVS8)

Alternative names: Leucine-rich repeat-containing protein 44

All UniProt accessions (4): A6PVS8, A6PVT2, A8MSG4, H0Y5F9

Isoforms (3)

UniProt ID	Names	Canonical?
A6PVS8-1	1	yes
A6PVS8-2	2
A6PVS8-3	3

RefSeq proteins (2): NP_001099129, NP_001309244 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001611	Leu-rich_rpt	Repeat
IPR032675	LRR_dom_sf	Homologous_superfamily
IPR052859	LRR-IQ_domain_protein	Family

UniProt features (20 total): sequence variant 7, splice variant 4, repeat 3, sequence conflict 2, domain 2, chain 1, coiled-coil region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A6PVS8-F1	70.18	0.36

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 40 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_UP, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN, DODD_NASOPHARYNGEAL_CARCINOMA_DN, KYNG_WERNER_SYNDROM_AND_NORMAL_AGING_DN, CREB3L4_TARGET_GENES, FOXJ2_TARGET_GENES, NAB2_TARGET_GENES, ZNF407_TARGET_GENES, MIR1277_5P, MIR513A_5P, MIR5003_3P, MIR4743_3P, GSE10240_IL17_VS_IL17_AND_IL22_STIM_PRIMARY_BRONCHIAL_EPITHELIAL_CELLS_DN, MIR499B_5P, MIR584_5P

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

835 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LRRIQ3	TMC7	Q7Z402	726
LRRIQ3	FPGT	O14772	705
LRRIQ3	SAMD5	Q5TGI4	670
LRRIQ3	FRMD3	A2A2Y4	645
LRRIQ3	V9GXZ4	V9GXZ4	627
LRRIQ3	TNNI3K	Q59H18	625
LRRIQ3	FAM227B	Q96M60	620
LRRIQ3	TMEM89	A2RUT3	507
LRRIQ3	FAM234B	A2RU67	479
LRRIQ3	USP17L11	C9JVI0	479
LRRIQ3	AMZ2	Q86W34	447
LRRIQ3	GARIN5A	Q6IPT2	434
LRRIQ3	PRAMEF15	P0DUQ1	433
LRRIQ3	SYT3	Q9BQG1	421
LRRIQ3	INTS4	Q96HW7	421

IntAct

13 interactions, top by confidence:

A	B	Type	Score
LRRIQ3	NCK2	psi-mi:“MI:0915”(physical association)	0.720
NCK2	LRRIQ3	psi-mi:“MI:0915”(physical association)	0.720
TNFAIP3	LRRIQ3	psi-mi:“MI:0914”(association)	0.420
TNFAIP3	LRRIQ3	psi-mi:“MI:2364”(proximity)	0.420
LRRIQ3	HNRNPU	psi-mi:“MI:0915”(physical association)	0.400
LRRIQ3	PGAM2	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (10): LRRIQ3 (Two-hybrid), R3HCC1L (Affinity Capture-MS), GNB4 (Affinity Capture-MS), R3HCC1L (Affinity Capture-MS), LRRIQ3 (Two-hybrid), HNRNPU (Proximity Label-MS), LRRIQ3 (Affinity Capture-RNA), PGAM2 (Affinity Capture-MS), LRRIQ3 (Cross-Linking-MS (XL-MS)), LRRIQ3 (Affinity Capture-Luminescence)

ESM2 similar proteins: A0A1B0GVH7, A6PVS8, A8DZJ1, A9Q751, D3ZSP7, D4AEC2, Q08AD1, Q08CX2, Q14DL3, Q2T9P0, Q2TA00, Q32KQ1, Q3UZ57, Q3V0J4, Q4G0U5, Q4R7B1, Q4R7Z7, Q5S003, Q5SUV2, Q5T1B0, Q5ZLS8, Q63164, Q66HC0, Q69CM7, Q6AXP3, Q6AYL8, Q6IRN6, Q6NXP0, Q6Q759, Q80X60, Q86WZ0, Q8C1B1, Q8C4J0, Q8C636, Q8CDN1, Q8CDU5, Q8IWF9, Q8N7B9, Q8N7U6, Q8ND61

Diamond homologs: A6PVS8, Q14DL3, Q6AYL8, Q9DAK8

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	84
Likely benign	12
Benign	5

Top pathogenic / likely-pathogenic (0)

SpliceAI

1628 predictions. Top by Δscore:

Variant	Effect	Δscore
1:74109386:ATACT:A	donor_loss	1.0000
1:74109387:TACTT:T	donor_loss	1.0000
1:74109388:ACTTA:A	donor_loss	1.0000
1:74109389:CTTA:C	donor_loss	1.0000
1:74109390:TTACA:T	donor_loss	1.0000
1:74109391:TA:T	donor_loss	1.0000
1:74109392:A:AC	donor_gain	1.0000
1:74109392:ACA:A	donor_loss	1.0000
1:74109393:C:CG	donor_gain	1.0000
1:74109393:CA:C	donor_gain	1.0000
1:74109393:CAT:C	donor_gain	1.0000
1:74109393:CATG:C	donor_gain	1.0000
1:74109393:CATGT:C	donor_gain	1.0000
1:74109549:CAGGG:C	acceptor_gain	1.0000
1:74026967:GATC:G	acceptor_loss	0.9900
1:74026968:ATCTA:A	acceptor_loss	0.9900
1:74026969:TCTA:T	acceptor_loss	0.9900
1:74026970:C:CC	acceptor_gain	0.9900
1:74026970:C:CG	acceptor_loss	0.9900
1:74026971:T:A	acceptor_loss	0.9900
1:74084058:T:C	donor_gain	0.9900
1:74109385:TATAC:T	donor_loss	0.9900
1:74109415:T:A	donor_gain	0.9900
1:74109536:T:C	acceptor_gain	0.9900
1:74109536:T:TC	acceptor_gain	0.9900
1:74109551:GGG:G	acceptor_gain	0.9900
1:74109552:GG:G	acceptor_gain	0.9900
1:74109554:C:CC	acceptor_gain	0.9900
1:74109558:A:AC	acceptor_gain	0.9900
1:74109558:A:C	acceptor_gain	0.9900

AlphaMissense

4170 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:74183455:A:G	L77P	0.995
1:74182731:A:G	L127P	0.994
1:74183449:A:G	L79P	0.994
1:74182809:A:G	L101P	0.993
1:74182834:A:G	W93R	0.993
1:74182834:A:T	W93R	0.993
1:74182706:G:C	S135R	0.991
1:74182706:G:T	S135R	0.991
1:74182708:T:G	S135R	0.991
1:74183439:A:C	N82K	0.991
1:74183439:A:T	N82K	0.991
1:74183505:A:C	N60K	0.991
1:74183505:A:T	N60K	0.991
1:74182659:A:T	L151H	0.990
1:74182688:T:A	R141S	0.990
1:74182688:T:G	R141S	0.990
1:74182800:A:G	L104P	0.990
1:74182806:A:G	L102P	0.990
1:74182715:A:C	C132W	0.988
1:74182734:G:T	A126D	0.988
1:74182790:A:C	N107K	0.988
1:74182790:A:T	N107K	0.988
1:74183455:A:T	L77H	0.987
1:74182659:A:G	L151P	0.986
1:74182717:A:G	C132R	0.986
1:74183522:A:G	C55R	0.986
1:74182689:C:G	R141T	0.984
1:74183464:A:G	L74S	0.984
1:74182589:G:C	F174L	0.983
1:74182589:G:T	F174L	0.983

dbSNP variants (sampled 300 via entrez): RS1000036156 (1:74182200 G>A), RS1000053646 (1:74101640 C>G,T), RS1000060888 (1:74124461 A>T), RS1000064626 (1:74038458 T>C), RS1000086014 (1:74079735 G>A), RS1000086324 (1:74182007 G>A), RS1000128915 (1:74173454 C>T), RS1000152690 (1:74188105 A>C,G), RS1000172039 (1:74062174 T>A), RS1000207147 (1:74190588 G>C,T), RS1000220447 (1:74133142 C>A,T), RS1000259683 (1:74176948 C>G), RS1000266100 (1:74106468 G>A), RS1000266271 (1:74095675 T>C), RS1000270640 (1:74098674 T>A,C)

Disease associations

OMIM: gene MIM:617957 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

18 associations (top):

Study	Trait	p-value
GCST000862_3	Bipolar disorder and schizophrenia	8.000000e-06
GCST001776_6	Cardiac Troponin-T levels	4.000000e-06
GCST002119_26	Metabolite levels (X-11787)	3.000000e-06
GCST002539_30	Schizophrenia	2.000000e-12
GCST002929_10	Chromium levels	5.000000e-06
GCST003986_8	Migraine	2.000000e-10
GCST004946_110	Schizophrenia	2.000000e-09
GCST005212_21	Asthma	7.000000e-06
GCST005950_6	Body mass index x sex x age interaction (4df test)	1.000000e-15
GCST005951_197	Body mass index	4.000000e-13
GCST005953_11	Body mass index (age <50)	3.000000e-15
GCST005954_3	Body mass index x age interaction	3.000000e-06
GCST006409_10	Allergic rhinitis	9.000000e-15
GCST007001_2	Cerebrospinal AB1-42 levels in normal cognition	9.000000e-07
GCST007327_193	Smoking status (ever vs never smokers)	2.000000e-11
GCST008810_38	Smoking initiation (ever regular vs never regular)	4.000000e-08
GCST009837_3	Anxiety	9.000000e-09
GCST011703_36	Smoking initiation	2.000000e-16

EFO canonical traits (9, from GWAS)

EFO ID	Trait name
EFO:0005043	cardiac troponin T measurement
EFO:0005276	hydroxy-leucine measurement
EFO:0004340	body mass index
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement
EFO:0004670	beta-amyloid 1-42 measurement
EFO:0004318	smoking behavior
EFO:0005670	smoking initiation
EFO:0009863	anxiety measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

17 total (human), top 17 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases expression	3
Tobacco Smoke Pollution	decreases expression, increases methylation	2
GSK-J4	decreases expression	1
methylmercuric chloride	decreases expression	1
bisphenol A	increases expression	1
hydroquinone	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine	decreases expression	1
licochalcone B	decreases expression	1
Lipopolysaccharides	affects response to substance, increases expression	1
Methyl Methanesulfonate	increases expression	1
Quercetin	decreases expression	1
Tetrachlorodibenzodioxin	increases expression	1
Cyclosporine	decreases expression	1
Aflatoxin B1	decreases methylation	1
Cadmium Chloride	decreases expression	1
Okadaic Acid	decreases expression	1

Clinical trials (associated diseases)

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