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QRICH2

gene
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Also known as DKFZP434P0316

Summary

QRICH2 (glutamine rich 2, HGNC:25326) is a protein-coding gene on chromosome 17q25.1, encoding Glutamine-rich protein 2 (Q9H0J4). Has an essential role in the formation of sperm flagella and flagellar structure maintainance.

Involved in cell projection assembly; flagellated sperm motility; and negative regulation of ubiquitin-dependent protein catabolic process. Located in sperm flagellum. Implicated in spermatogenic failure 35.

Source: NCBI Gene 84074 — RefSeq curated summary.

At a glance

  • Gene–disease (curated): spermatogenic failure 35 (Strong, GenCC)
  • GWAS associations: 10
  • Clinical variants (ClinVar): 373 total — 5 pathogenic, 6 likely-pathogenic
  • Phenotypes (HPO): 7
  • MANE Select transcript: NM_001388453

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:25326
Approved symbolQRICH2
Nameglutamine rich 2
Location17q25.1
Locus typegene with protein product
StatusApproved
AliasesDKFZP434P0316
Ensembl geneENSG00000129646
Ensembl biotypeprotein_coding
OMIM618304
Entrez84074

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 5 protein_coding, 1 nonsense_mediated_decay

ENST00000262765, ENST00000447564, ENST00000524722, ENST00000532549, ENST00000636395, ENST00000680821

RefSeq mRNA: 2 — MANE Select: NM_001388453 NM_001388453, NM_032134

CCDS: CCDS32741, CCDS92399

Canonical transcript exons

ENST00000680821 — 19 exons

ExonStartEnd
ENSE000016582657629101576294021
ENSE000017666557630488276304941
ENSE000017963887630441576304525
ENSE000035044517627581976275947
ENSE000035051507628065476280728
ENSE000035159167627936376279428
ENSE000035278417628999276290077
ENSE000035322297628780076287897
ENSE000035540427627716376277310
ENSE000035625597628719276287306
ENSE000036018237628083176280953
ENSE000036037107628003376280154
ENSE000036077647628028776280451
ENSE000036152207628186476282115
ENSE000036326417627798976278189
ENSE000036768117627668076276767
ENSE000036880217627904176279142
ENSE000039138997627404976274260
ENSE000039161017630746576308276

Expression profiles

Bgee: expression breadth ubiquitous, 162 present calls, max score 88.11.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0110 / max 13.5325, expressed in 3 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter IDTPM avgSamples expressed
1681990.01103

Top tissues by expression

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

TissueAnatomy IDExpression scoreQuality
left testisUBERON:000453388.11gold quality
right testisUBERON:000453487.60gold quality
lower esophagus mucosaUBERON:003583485.40gold quality
testisUBERON:000047384.73gold quality
right lobe of thyroid glandUBERON:000111980.79gold quality
ventricular zoneUBERON:000305379.61gold quality
stromal cell of endometriumCL:000225579.55gold quality
cerebellar hemisphereUBERON:000224579.55gold quality
right hemisphere of cerebellumUBERON:001489079.48gold quality
cerebellar cortexUBERON:000212979.45gold quality
left lobe of thyroid glandUBERON:000112078.74gold quality
sural nerveUBERON:001548878.55gold quality
cortical plateUBERON:000534378.43gold quality
cerebellumUBERON:000203778.02gold quality
thyroid glandUBERON:000204677.30gold quality
ganglionic eminenceUBERON:000402377.07gold quality
male germ line stem cell (sensu Vertebrata) in testisCL:0000089 ∩ UBERON:000047376.25gold quality
right frontal lobeUBERON:000281076.23gold quality
mucosa of transverse colonUBERON:000499175.57gold quality
anterior cingulate cortexUBERON:000983575.42gold quality
hypothalamusUBERON:000189874.87gold quality
putamenUBERON:000187474.57gold quality
Brodmann (1909) area 9UBERON:001354074.43gold quality
nucleus accumbensUBERON:000188274.10gold quality
caudate nucleusUBERON:000187373.83gold quality
minor salivary glandUBERON:000183073.64gold quality
C1 segment of cervical spinal cordUBERON:000646973.17gold quality
right lobe of liverUBERON:000111472.95gold quality
saliva-secreting glandUBERON:000104472.67gold quality
primordial germ cell in gonadCL:0000670 ∩ UBERON:000099172.40gold quality

Single-cell (SCXA)

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

ExperimentMarker?Max mean expression
E-ANND-3no3.75

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

5 targeting QRICH2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNAMax scoreAvg scoremiRNA target_count
HSA-MIR-3140-5P99.3969.041136
HSA-MIR-6731-5P99.2867.422375
HSA-MIR-808599.2867.562362
HSA-MIR-660-3P98.1466.041434
HSA-MIR-57285.6259.3430

Literature-anchored findings (GeneRIF, showing 3)

  • The findings strongly suggest that the genetic mutations of QRICH2 can lead to male infertility with multiple morphological abnormalities of the flagella, and that QRICH2 is essential for sperm flagellar formation. (PMID:30683861)
  • Whole exome sequencing of men with multiple morphological abnormalities of the sperm flagella reveals novel homozygous QRICH2 mutations. (PMID:31292949)
  • Loss-of-function missense variant of AKAP4 induced male infertility through reduced interaction with QRICH2 during sperm flagella development. (PMID:34415320)

Cross-species orthologs

2 orthologs

OrganismSymbolGene ID
mus_musculusQrich2ENSMUSG00000070331
rattus_norvegicusQrich2ENSRNOG00000025254

Paralogs (4): ZP2 (ENSG00000103310), ZP4 (ENSG00000116996), ZP1 (ENSG00000149506), C16orf96 (ENSG00000205832)

Protein

Protein identifiers

Glutamine-rich protein 2 — Q9H0J4 (reviewed: Q9H0J4)

All UniProt accessions (6): Q9H0J4, A0A1B0GW36, A0A7P0T7G7, E9PPH7, H0YDB9, H7C0E3

UniProt curated annotations — full annotation on UniProt →

Function. Has an essential role in the formation of sperm flagella and flagellar structure maintainance. It acts as a suppressor of ubiquitination and degradation of proteins involved in flagellar development and motility.

Subunit / interactions. Interacts with AKAP3, ODF2 and TSSK4. Interacts with AKAP4. Interacts with CFAP70.

Subcellular location. Nucleus membrane. Nucleus. Cytoplasm. Cell projection. Cilium. Flagellum.

Tissue specificity. Expressed in the sperm.

Disease relevance. Spermatogenic failure 35 (SPGF35) [MIM:618341] An autosomal recessive infertility disorder caused by spermatogenesis defects that result in multiple abnormalities of sperm flagellum and severely impaired spermatozoa motility. The disease is caused by variants affecting the gene represented in this entry.

Isoforms (3)

UniProt IDNamesCanonical?
Q9H0J4-11yes
Q9H0J4-22
Q9H0J4-33

RefSeq proteins (2): NP_001375382, NP_115510 (=MANE)

Domains & families (InterPro)

IDNameType
IPR032013DUF4795Domain

Pfam: PF16043

UniProt features (37 total): sequence variant 17, compositionally biased region 8, region of interest 6, splice variant 3, coiled-coil region 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-Q9H0J4-F145.380.00

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 55 (showing top): GOBP_NEGATIVE_REGULATION_OF_PROTEOLYSIS, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_REGULATION_OF_CATABOLIC_PROCESS, GOBP_CILIUM_MOVEMENT, GOBP_CILIUM_OR_FLAGELLUM_DEPENDENT_CELL_MOTILITY, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_METABOLIC_PROCESS, GOBP_CELL_PROJECTION_ORGANIZATION, GOBP_REGULATION_OF_PROTEOLYSIS, GOBP_PROTEIN_CATABOLIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_CATABOLIC_PROCESS, GOCC_NUCLEAR_ENVELOPE, GOCC_MOTILE_CILIUM, GOBP_PROTEOLYSIS, GOCC_NUCLEAR_MEMBRANE, GOCC_CILIUM

GO Biological Process (3): cell projection assembly (GO:0030031), flagellated sperm motility (GO:0030317), negative regulation of ubiquitin-dependent protein catabolic process (GO:2000059)

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

GO Cellular Component (8): cytoplasm (GO:0005737), nuclear membrane (GO:0031965), sperm flagellum (GO:0036126), nucleus (GO:0005634), cilium (GO:0005929), membrane (GO:0016020), motile cilium (GO:0031514), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
cellular anatomical structure3
cellular component assembly1
cell projection organization1
cilium-dependent cell motility1
cilium movement involved in cell motility1
sperm motility1
ubiquitin-dependent protein catabolic process1
negative regulation of protein catabolic process1
regulation of ubiquitin-dependent protein catabolic process1
binding1
intracellular anatomical structure1
nucleus1
nuclear envelope1
organelle membrane1
9+2 motile cilium1
intracellular membrane-bounded organelle1
intraciliary transport particle1
membrane-bounded organelle1
plasma membrane bounded cell projection1
cilium1

Protein interactions and networks

STRING

1149 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
QRICH2CFAP44Q96MT7795
QRICH2CFAP43Q8NDM7794
QRICH2QRICH1Q2TAL8734
QRICH2CFAP69A5D8W1706
QRICH2ARMC2Q8NEN0687
QRICH2DNAH1Q9P2D7686
QRICH2TTC21AQ8NDW8670
QRICH2CFAP251Q8TBY9640
QRICH2TTC29Q8NA56636
QRICH2CFAP70Q5T0N1616
QRICH2FSIP2Q5CZC0600
QRICH2CCDC39Q9UFE4596
QRICH2DNAH17Q9UFH2591
QRICH2SPEF2Q9C093583
QRICH2CFAP58Q5T655581

IntAct

14 interactions, top by confidence:

ABTypeScore
KMT2BMEN1psi-mi:“MI:0914”(association)0.460
KLHL22TRAV18psi-mi:“MI:0914”(association)0.350
MPDU1QRICH2psi-mi:“MI:0915”(physical association)0.000
NUP98QRICH2psi-mi:“MI:0915”(physical association)0.000
PANK2QRICH2psi-mi:“MI:0915”(physical association)0.000
EIPR1QRICH2psi-mi:“MI:0915”(physical association)0.000
QRICH2psi-mi:“MI:0915”(physical association)0.000
MAGEB2QRICH2psi-mi:“MI:0915”(physical association)0.000
ZNRD2QRICH2psi-mi:“MI:0915”(physical association)0.000
GAPDHQRICH2psi-mi:“MI:0915”(physical association)0.000
SNAI1QRICH2psi-mi:“MI:0915”(physical association)0.000
DISC1QRICH2psi-mi:“MI:0915”(physical association)0.000

BioGRID (9): QRICH2 (Affinity Capture-MS), QRICH2 (Affinity Capture-MS), QRICH2 (Affinity Capture-MS), QRICH2 (Affinity Capture-MS), QRICH2 (Affinity Capture-MS), QRICH2 (Affinity Capture-MS), QRICH2 (Affinity Capture-MS), QRICH2 (Affinity Capture-RNA), QRICH2 (Affinity Capture-MS)

ESM2 similar proteins: A0A1B0GUY1, A6NJ88, A6QL64, B3KS81, E9Q6E9, O43493, O48582, O77733, P04279, P0C7A4, P0C7A5, P0CV57, P0DKJ7, P10322, P16225, P48997, P48998, Q02383, Q06990, Q08AG5, Q0ZNK1, Q5JPF3, Q5JRC9, Q5SRN2, Q5U7M7, Q5U7M8, Q5U7M9, Q5U7N0, Q5U7N1, Q5U7N3, Q5U7N4, Q5XHX6, Q659K0, Q6AYN3, Q6JHY2, Q6P902, Q6SJ82, Q6X2M3, Q6XPR3, Q80Y39

Diamond homologs: A6NNT2, E9QMW4, Q3V2A7, Q9H0J4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

ClassificationCount (floor)
Pathogenic5
Likely pathogenic6
Uncertain significance231
Likely benign59
Benign41

Top pathogenic / likely-pathogenic (11)

Variant IDHGVSClassification
619117NM_001388453.1(QRICH2):c.690G>A (p.Trp230Ter)Pathogenic
619118NM_001388453.1(QRICH2):c.3535C>T (p.Arg1179Ter)Pathogenic
815953GRCh37/hg19 17q25.1-25.3(chr17:73261871-78608763)x3Pathogenic
974676NM_001388453.1(QRICH2):c.3999C>G (p.Tyr1333Ter)Pathogenic
974677NM_001388453.1(QRICH2):c.5112C>G (p.Tyr1704Ter)Pathogenic
1298725NM_001388453.1(QRICH2):c.5266-2A>GLikely pathogenic
2630353NM_001388453.1(QRICH2):c.4914dup (p.Asn1639fs)Likely pathogenic
3356262NM_001388453.1(QRICH2):c.5482+1G>ALikely pathogenic
3780515NM_001388453.1(QRICH2):c.5171dup (p.Ser1725fs)Likely pathogenic
3892239NM_001388453.1(QRICH2):c.1507C>T (p.Gln503Ter)Likely pathogenic
3892240NM_001388453.1(QRICH2):c.3952_3953del (p.Arg1318fs)Likely pathogenic

SpliceAI

3381 predictions. Top by Δscore:

VariantEffectΔscore
17:76275948:CT:Cacceptor_loss1.0000
17:76276678:A:ACdonor_gain1.0000
17:76276678:ACTGT:Adonor_gain1.0000
17:76276679:C:CCdonor_gain1.0000
17:76276679:CT:Cdonor_gain1.0000
17:76276679:CTGT:Cdonor_gain1.0000
17:76276679:CTGTC:Cdonor_gain1.0000
17:76276764:CATG:Cacceptor_gain1.0000
17:76276766:TG:Tacceptor_gain1.0000
17:76276768:C:CCacceptor_gain1.0000
17:76277309:CC:Cacceptor_gain1.0000
17:76277310:CC:Cacceptor_gain1.0000
17:76277311:C:CCacceptor_gain1.0000
17:76278041:T:Cdonor_gain1.0000
17:76278197:G:Cacceptor_gain1.0000
17:76278197:G:GCacceptor_gain1.0000
17:76279039:A:ACdonor_gain1.0000
17:76279040:C:CCdonor_gain1.0000
17:76279141:CA:Cacceptor_gain1.0000
17:76279143:C:CCacceptor_gain1.0000
17:76279361:A:ACdonor_gain1.0000
17:76279362:C:CCdonor_gain1.0000
17:76280028:CTCA:Cdonor_loss1.0000
17:76280029:TCA:Tdonor_loss1.0000
17:76280030:CA:Cdonor_loss1.0000
17:76280031:A:ACdonor_gain1.0000
17:76280031:A:ATdonor_loss1.0000
17:76280031:ACCT:Adonor_gain1.0000
17:76280032:C:CCdonor_gain1.0000
17:76280032:CCT:Cdonor_gain1.0000

AlphaMissense

12279 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
17:76279406:A:GC1425R0.998
17:76279404:G:CC1425W0.997
17:76279396:C:TC1428Y0.996
17:76279405:C:GC1425S0.995
17:76279405:C:TC1425Y0.995
17:76279406:A:TC1425S0.995
17:76279410:G:CF1423L0.995
17:76279410:G:TF1423L0.995
17:76279412:A:GF1423L0.995
17:76281928:A:GL1234P0.995
17:76280384:A:GL1344P0.994
17:76280889:A:GL1277P0.994
17:76282105:A:GL1175P0.994
17:76279396:C:GC1428S0.993
17:76279397:A:GC1428R0.993
17:76279397:A:TC1428S0.993
17:76280868:A:GL1284P0.993
17:76279395:A:CC1428W0.992
17:76279396:C:AC1428F0.991
17:76280363:A:GL1351P0.991
17:76279405:C:AC1425F0.990
17:76287277:A:GL1143P0.990
17:76279390:C:GR1430P0.989
17:76279411:A:GF1423S0.989
17:76280106:A:GW1393R0.989
17:76280106:A:TW1393R0.989
17:76304447:C:GA59P0.989
17:76276728:A:CY1603D0.988
17:76287202:A:GL1168P0.988
17:76304455:A:GL56P0.988

dbSNP variants (sampled 300 via entrez): RS1000058997 (17:76306931 G>A), RS1000266899 (17:76311518 C>G), RS1000272203 (17:76310421 C>T), RS1000334016 (17:76277858 TTCTC>T,TTC,TTCTCTC), RS1000401798 (17:76282925 T>G), RS1000508785 (17:76305042 C>A,T), RS1000554076 (17:76308953 G>T), RS1000558377 (17:76276875 G>A), RS1000607739 (17:76308768 G>C), RS1000658046 (17:76289926 G>T), RS1000687718 (17:76289632 A>G), RS1000791018 (17:76286957 G>A,T), RS1000941874 (17:76281273 G>A), RS1001142229 (17:76281562 G>A), RS1001200875 (17:76296437 G>C)

Disease associations

OMIM: gene MIM:618304 | disease phenotypes: MIM:618341

GenCC curated gene-disease

DiseaseClassificationInheritance
spermatogenic failure 35StrongAutosomal recessive

Mondo (1): spermatogenic failure 35 (MONDO:0032686)

Orphanet (0):

HPO phenotypes

7 total (7 of 7 shown, HPO-id order):

HPOTerm
HP:0000007Autosomal recessive inheritance
HP:0003251Male infertility
HP:0011462Young adult onset
HP:0032558Absent sperm flagella
HP:0032559Short sperm flagella
HP:0032560Coiled sperm flagella
HP:0033525Absent sperm axoneme central pair complex

GWAS associations

10 associations (top):

StudyTraitp-value
GCST001791_20Urate levels2.000000e-07
GCST003245_5White matter hyperintensities in ischemic stroke1.000000e-06
GCST007733_21Serum uric acid levels2.000000e-07
GCST008971_116Urate levels6.000000e-08
GCST008972_22Urate levels1.000000e-10
GCST010173_86Triglyceride levels2.000000e-10
GCST010244_153Triglyceride levels1.000000e-11
GCST010637_26Urate levels4.000000e-08
GCST90020025_1462Waist-to-hip ratio adjusted for BMI1.000000e-10
GCST90020027_587Waist-hip index2.000000e-10

EFO canonical traits (5, from GWAS)

EFO IDTrait name
EFO:0004531urate measurement
EFO:0005665white matter hyperintensity measurement
EFO:0004761uric acid measurement
EFO:0004530triglyceride measurement
EFO:0007788BMI-adjusted waist-hip ratio

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

ChemicalActions (top 5)PubMed papers
aristolochic acid Iincreases expression1
2,5,2’,5’-tetrachlorobiphenyldecreases expression1
sulforaphaneincreases expression1
sodium arsenitedecreases expression1
benzo(e)pyreneaffects methylation1
CGP 52608affects binding, increases reaction1
abrinedecreases expression1
bisphenol Sdecreases expression1
jinfukangdecreases expression, affects cotreatment1
Air Pollutantsincreases abundance, increases expression1
Arsenicaffects methylation1
Benzo(a)pyreneaffects methylation1
Cisplatinaffects cotreatment, decreases expression1
Methapyrileneaffects methylation1
Quercetinincreases expression1
Rotenonedecreases expression1
Smokedecreases expression1
Thiramincreases expression1
Urethaneincreases expression1
Valproic Acidincreases methylation1
Aflatoxin B1increases methylation1
Cadmium Chlorideincreases expression1
Particulate Matterincreases abundance, increases expression1

Clinical trials (associated diseases)

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

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
v1.1.4
BioBTree
v2.0.2

Sources 74

This page pulls from 74 datasets indexed by BioBTree:

alphafoldalphamissenseantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticsccdscellosauruschembl_activitychembl_targetciviccivic_evidenceclingen_dosageclingen_gene_validityclinical_trialsclinvarcollectrictd_gene_interactiondbsnpdepmapdiamond_similarityefoensemblentrezesm2_similarityexonfantom5_genefantom5_promotergenccgenerifgogoparentgtopdbgwasgwas_studyhgnchpointactinterprointogenjasparmeshmimmirdbmondomsigdborphanetorthologparalogpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assaypubmedreactomerefseqrhearnacentralscxa_expressionscxa_gene_experimentsignorspliceaistring_interactiontranscriptufeatureuniprot