IQCF5

Summary

IQCF5 (IQ motif containing F5, HGNC:35159) is a protein-coding gene on chromosome 3p21.2, encoding IQ domain-containing protein F5 (A8MTL0).

Predicted to enable calmodulin binding activity.

Source: NCBI Gene 389124 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 25 total
• MANE Select transcript: NM_001145059

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:35159
Approved symbol	IQCF5
Name	IQ motif containing F5
Location	3p21.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000214681
Ensembl biotype	protein_coding
Entrez	389124

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000446461

RefSeq mRNA: 1 — MANE Select: NM_001145059 NM_001145059

CCDS: CCDS46838

Canonical transcript exons

ENST00000446461 — 2 exons

Exon	Start	End
ENSE00001728282	51875528	51875601
ENSE00001749844	51873721	51874175

Expression profiles

Bgee: expression breadth broad, 26 present calls, max score 97.58.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0562 / max 61.7986, expressed in 3 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
42368	0.0562	3

Top tissues by expression

202 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	97.58	gold quality
sperm	CL:0000019	97.22	gold quality
left testis	UBERON:0004533	95.19	gold quality
right testis	UBERON:0004534	95.07	gold quality
testis	UBERON:0000473	91.77	gold quality
adult organism	UBERON:0007023	81.63	gold quality
pancreatic ductal cell	CL:0002079	62.83	silver quality
myocardium	UBERON:0002349	56.78	gold quality
epithelial cell of pancreas	CL:0000083	54.99	gold quality
cardiac muscle of right atrium	UBERON:0003379	54.34	gold quality
left ventricle myocardium	UBERON:0006566	54.23	gold quality
epithelium of mammary gland	UBERON:0003244	54.09	gold quality
mammary duct	UBERON:0001765	54.05	gold quality
kidney epithelium	UBERON:0004819	53.93	gold quality
upper arm skin	UBERON:0004263	53.52	gold quality
heart right ventricle	UBERON:0002080	53.21	gold quality
tibialis anterior	UBERON:0001385	52.42	silver quality
deltoid	UBERON:0001476	52.25	gold quality
parotid gland	UBERON:0001831	52.14	gold quality
lower lobe of lung	UBERON:0008949	48.86	silver quality
nasal cavity epithelium	UBERON:0005384	48.75	gold quality
ileal mucosa	UBERON:0000331	48.43	silver quality
quadriceps femoris	UBERON:0001377	48.14	gold quality
vastus lateralis	UBERON:0001379	46.76	gold quality
layer of synovial tissue	UBERON:0007616	46.13	gold quality
subthalamic nucleus	UBERON:0001906	44.58	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	43.37	gold quality
biceps brachii	UBERON:0001507	42.97	gold quality
upper leg skin	UBERON:0004262	42.72	silver quality
secondary oocyte	CL:0000655	42.57	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.08

Regulation

Is transcription factor: no

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Iqcf5	ENSMUSG00000066382
rattus_norvegicus	Iqcf5	ENSRNOG00000013164

Paralogs (4): IQCF1 (ENSG00000173389), IQCF2 (ENSG00000184345), IQCF6 (ENSG00000214686), IQCF3 (ENSG00000229972)

Protein

Protein identifiers

IQ domain-containing protein F5 — A8MTL0 (reviewed: A8MTL0)

All UniProt accessions (1): A8MTL0

RefSeq proteins (1): NP_001138531* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000048	IQ_motif_EF-hand-BS	Binding_site
IPR039887	IQCF	Family

Pfam: PF00612

UniProt features (4 total): domain 2, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A8MTL0-F1	93.19	0.74

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 23 (showing top): KASLER_HDAC7_TARGETS_1_UP, chr3p21, GSE10856_CTRL_VS_TNFRSF6B_IN_MACROPHAGE_DN, GSE13306_RA_VS_UNTREATED_TCONV_DN, GSE13485_DAY3_VS_DAY7_YF17D_VACCINE_PBMC_UP, GSE13485_PRE_VS_POST_YF17D_VACCINATION_PBMC_UP, HBZ_TARGET_GENES, GSE7460_TREG_VS_TCONV_ACT_DN, GSE7460_FOXP3_MUT_VS_WT_ACT_TCONV_DN, GSE7460_FOXP3_MUT_VS_HET_ACT_TCONV_UP, GSE7460_WT_VS_FOXP3_HET_ACT_TCONV_UP, GSE1112_OT1_CD8AB_VS_HY_CD8AA_THYMOCYTE_RTOC_CULTURE_UP, GSE2585_CD80_HIGH_VS_LOW_AIRE_KO_MTEC_DN, GSE5589_LPS_VS_LPS_AND_IL10_STIM_IL10_KO_MACROPHAGE_180MIN_DN, ODONNELL_TFRC_TARGETS_UP

GO Biological Process (0):

GO Molecular Function (2): calmodulin binding (GO:0005516), protein binding (GO:0005515)

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein binding	1
binding	1

Protein interactions and networks

STRING

180 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IQCF5	TMEM89	A2RUT3	713
IQCF5	SPATA31F1	Q6ZU69	581
IQCF5	HAPLN4	Q86UW8	558
IQCF5	LRRCC1	Q9C099	557
IQCF5	CENPM	Q9NSP4	500
IQCF5	OAZ3	Q9UMX2	475
IQCF5	ABHD14A	Q9BUJ0	463
IQCF5	KRTAP10-11	P60412	418
IQCF5	FSIP2	Q5CZC0	404
IQCF5	KRTAP10-1	P60331	369
IQCF5	ULK4	Q96C45	356
IQCF5	PHOX2B	Q99453	327
IQCF5	SSTR1	P30872	318
IQCF5	IQCJ	Q1A5X6	310
IQCF5	GSTM5	P46439	305

IntAct

3 interactions, top by confidence:

A	B	Type	Score
HMGB4	IQCF5	psi-mi:“MI:0915”(physical association)	0.400
USP8	IQCF5	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (7): USP8 (Proximity Label-MS), HMGB4 (Proximity Label-MS), ARHGEF2 (Cross-Linking-MS (XL-MS)), RPS6 (Cross-Linking-MS (XL-MS)), IQCF5 (Cross-Linking-MS (XL-MS)), IQCF5 (Cross-Linking-MS (XL-MS)), IQCF5 (Protein-peptide)

ESM2 similar proteins: A1A5Q7, A4D126, A4II32, A6NCI4, A8K8P3, A8MTL0, A8MYZ5, A9CB34, E0CYC6, F1QWK4, O14772, O15554, O89109, P0C7M6, P0C8N6, Q05AA6, Q08CB3, Q13474, Q1HAQ0, Q1LWG4, Q2M2U5, Q32KU4, Q3SYS7, Q3TFD2, Q3UVV9, Q4AC99, Q5I0I4, Q5R796, Q5RFS1, Q8BHD4, Q8BP00, Q8BPW0, Q8CB65, Q8CHT6, Q8IXL9, Q8K2I9, Q8N0W5, Q8N6M8, Q8NEA4, Q8NF37

Diamond homologs: A8MTL0, A8MYZ5, P0C7M6, Q2M2U5, Q32KU4, Q3SYS7, Q6AXX0, Q8IXL9, Q8N6M8, Q9D498, Q9D9K8, Q9DAL7

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	25
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

385 predictions. Top by Δscore:

Variant	Effect	Δscore
3:51874177:T:C	acceptor_gain	1.0000
3:51874175:CCT:C	acceptor_gain	0.9900
3:51874176:C:CC	acceptor_gain	0.9900
3:51874177:T:TC	acceptor_gain	0.9900
3:51874175:CC:C	acceptor_loss	0.9800
3:51874176:CTT:C	acceptor_loss	0.9800
3:51874174:GC:G	acceptor_gain	0.9400
3:51874176:C:T	acceptor_gain	0.9400
3:51874180:C:CT	acceptor_gain	0.9400
3:51875166:C:A	donor_gain	0.9400
3:51875425:A:AC	donor_gain	0.9200
3:51875426:C:CC	donor_gain	0.9200
3:51875553:A:AC	donor_gain	0.9100
3:51874173:GGC:G	acceptor_gain	0.8900
3:51874181:A:T	acceptor_gain	0.8900
3:51875467:CAAAA:C	donor_gain	0.8900
3:51875466:A:AC	donor_gain	0.8700
3:51875467:C:CC	donor_gain	0.8700
3:51875343:A:AC	donor_gain	0.8600
3:51875344:C:CC	donor_gain	0.8600
3:51875339:T:A	donor_gain	0.8500
3:51875165:T:TA	donor_gain	0.8400
3:51874172:GGGCC:G	acceptor_gain	0.8300
3:51874406:TACC:T	acceptor_gain	0.8300
3:51875426:CT:C	donor_gain	0.8300
3:51874171:TGGGC:T	acceptor_gain	0.8200
3:51874400:CCTA:C	acceptor_gain	0.8200
3:51875425:ACTCT:A	donor_gain	0.8100
3:51875426:CTCT:C	donor_gain	0.8100
3:51875426:CTCTC:C	donor_gain	0.8100

AlphaMissense

965 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:51873940:C:A	M80I	0.879
3:51873940:C:G	M80I	0.879
3:51873940:C:T	M80I	0.879
3:51874116:A:G	W22R	0.874
3:51874116:A:T	W22R	0.874
3:51874047:A:G	W45R	0.860
3:51874047:A:T	W45R	0.860
3:51873945:G:T	R79S	0.854
3:51873944:C:G	R79P	0.853
3:51874112:C:G	R23P	0.844
3:51873921:A:C	Y87D	0.836
3:51873903:C:G	A93P	0.830
3:51873955:C:A	Q75H	0.821
3:51873955:C:G	Q75H	0.821
3:51874122:C:G	A20P	0.821
3:51873794:A:G	I129T	0.815
3:51874045:C:A	W45C	0.808
3:51874045:C:G	W45C	0.808
3:51874058:A:G	I41T	0.808
3:51874123:C:A	Q19H	0.808
3:51874123:C:G	Q19H	0.808
3:51874080:C:G	A34P	0.805
3:51874094:C:G	R29P	0.794
3:51874054:C:A	Q42H	0.793
3:51874054:C:G	Q42H	0.793
3:51873929:C:G	R84P	0.790
3:51874127:A:G	I18T	0.790
3:51874097:C:G	R28P	0.779
3:51873920:T:G	Y87S	0.776
3:51873886:C:A	Q98H	0.774

dbSNP variants (sampled 300 via entrez): RS1001039892 (3:51876690 G>A), RS1001210895 (3:51873303 T>C), RS1002923600 (3:51874066 A>G), RS1002978122 (3:51874601 T>C), RS1004426610 (3:51874114 C>A,T), RS1004661100 (3:51876054 T>G), RS1006431473 (3:51877331 T>C), RS1006932272 (3:51876505 G>T), RS1007884923 (3:51877083 T>C), RS1007937029 (3:51876764 C>G,T), RS1008935031 (3:51875412 C>G), RS1010251 (3:51874741 A>T), RS1010277382 (3:51873368 A>G), RS1010556059 (3:51875386 A>G,T), RS1010610166 (3:51875055 C>A,T)

Disease associations

OMIM: gene `` | disease phenotypes: MIM:142623

GenCC curated gene-disease

Mondo (1): Hirschsprung disease (MONDO:0018309)

Orphanet (1): Hirschsprung disease (Orphanet:388)

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST002337_51	Amyotrophic lateral sclerosis (sporadic)	2.000000e-09

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D006627	Hirschsprung Disease	C06.198.439; C06.405.469.158.701.439; C16.131.314.439

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

1 total (human), top 1 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases expression	2

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02343562	PHASE4	UNKNOWN	Probiotics for Prophylaxis of Postoperative Hirschsprungs Associated Enterocolitis
NCT07186647	PHASE4	COMPLETED	Laparoscopic-Assisted Transanal Pull-Through for Hirschsprung Disease in Pediatric:Short and Intermediate Outcomes of Two Different Techniques
NCT03660176	PHASE3	UNKNOWN	Effects of Butyrate Enemas on Postoperative Intestinal Mobility Disorders in Hirschsprung’s Disease
NCT04904081	PHASE3	UNKNOWN	Feasibility of Use of Indocyanine Green in Pediatric Colorectal Surgery
NCT00630838	PHASE2	COMPLETED	Probiotic Prophylaxis of Hirschprung’s Disease Associated Enterocolitis (HAEC)
NCT00671684	PHASE1/PHASE2	UNKNOWN	Endoscopic Mucosal Resection (EMR) for Diagnosis of Hirschsprung’s Disease
NCT01985646	EARLY_PHASE1	COMPLETED	A Trial on Conservative Treatment for Infants’ Hirschsprung Disease
NCT00478712	Not specified	RECRUITING	Hirschsprung Disease Genetic Study
NCT01515501	Not specified	COMPLETED	Endoscopic Mucosal Resection for the Diagnosis of a-Ganglionosis, a Controlled Prospective Trial (EDGE Trial)
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
NCT01927809	Not specified	UNKNOWN	Genetic Mosaicism in Hirschsprung’s Disease
NCT02193685	Not specified	UNKNOWN	Identification Genetic, Immunologic and Microbial Markers of Hirschsprung Associated Enterocolitis in Children With Hirschsprung Disease
NCT02216994	Not specified	UNKNOWN	A New Scoring System Improves Diagnostic Accuracy of Intestinal Dysganglionosis –a Prospective Study
NCT02296008	Not specified	COMPLETED	3D High Resolution Anorectal Manometry in Children After Surgery for Anorectal Disorders
NCT02776176	Not specified	UNKNOWN	Enhanced Recovery After Surgery In Hirschsprung Disease
NCT02857205	Not specified	COMPLETED	MICROPRUNG : Intestinal Microbiota Analysis in Patients With or Without Hirschsprung’s Associated EnteroColitis
NCT03269812	Not specified	UNKNOWN	Laparoscopic Assisted Pull-through Versus Other Surgical Procedures for Treatment of Hirschsprung Disease
NCT03406741	Not specified	COMPLETED	Neuropsychological Development and Functional Outcome Sin Children With Hirschsprung Disease at School Age
NCT03626350	Not specified	ACTIVE_NOT_RECRUITING	Prospective Evaluation of the Efficacy and Safety of Submucosal Endoscopy
NCT03666767	Not specified	COMPLETED	Management and Outcomes of Congenital Anomalies in Low-, Middle- and High-Income Countries
NCT04020939	Not specified	COMPLETED	The Role of Indocyanine Green Angiography Fluorescence on Intestinal Resections in Pediatric Surgery.
NCT04106947	Not specified	UNKNOWN	Transition of Care for Patients With Hirschsprung Disease and Anorectal Malformations
NCT04149093	Not specified	UNKNOWN	The Association Between Calretinin and the Function of Ganglion Cells in Hirschsprung Disease
NCT04150120	Not specified	COMPLETED	eHealth as an Aid for Facilitating and Supporting Self-management in Families With Long-term Childhood Illness
NCT04213976	Not specified	UNKNOWN	Ostomy in Continuity or Conventional Ileostomy: a Retrospective Multicentric Analysis
NCT04476225	Not specified	COMPLETED	Induced Pluripotent Stem Cells for Disease Research
NCT04598841	Not specified	COMPLETED	Nutrition Support for Hirschsprung Disease
NCT04622410	Not specified	RECRUITING	Registry for Hirschsprung Disease of the BELAPS
NCT04624334	Not specified	TERMINATED	Non-invasive Assessment of Colonic Motility
NCT04713085	Not specified	COMPLETED	Sacral Neuromodulation in Children and Adolescents
NCT04730128	Not specified	COMPLETED	Translation and Validation of a Disease-specific Questionnaire for Hirschsprung’s Disease in Danish Patients
NCT04837963	Not specified	COMPLETED	Does Hirschsprung Disease Increase the Risk of Febrile Urinary Tract Infection in Children
NCT04957667	Not specified	COMPLETED	Scintigraphic Defecography for Evaluation of Functional Outcome in an Adult Hirschsprung Population
NCT05038345	Not specified	TERMINATED	Hirschsprung Disease Trends in the United States: Analysis of the National Inpatient Sample
NCT05044741	Not specified	COMPLETED	Risk Factors of Perforated HSCR in Neonates
NCT05293353	Not specified	UNKNOWN	Neokare Safety and Tolerability Assessment in Neonates With GI Problems
NCT05307419	Not specified	UNKNOWN	Full Thickness vs. Rectal Suction Biopsy in the Diagnosis of Hirschsprungs Disease
NCT05450991	Not specified	RECRUITING	Long-term Qualitative and Quantitative Outcomes of Children With Hirschsprung’s Disease and Anorectal Malformations
NCT05655845	Not specified	UNKNOWN	Risk Factors for Bowel Dysfunction at Preschool and Early Childhood Age in Children With Hirschsprung Disease
NCT06072976	Not specified	RECRUITING	The Influence of Feeding Source on the Gut Microbiome and Time to Full Feeds in Neonates With Congenital Gastrointestinal Pathologies