HEATR4

Summary

HEATR4 (HEAT repeat containing 4, HGNC:16761) is a protein-coding gene on chromosome 14q24.3, encoding HEAT repeat-containing protein 4 (Q86WZ0).

Predicted to enable oxidoreductase activity.

Source: NCBI Gene 399671 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 41 total
• MANE Select transcript: NM_001220484

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16761
Approved symbol	HEATR4
Name	HEAT repeat containing 4
Location	14q24.3
Locus type	gene with protein product
Status	Approved
Aliases	MGC48595
Ensembl gene	ENSG00000187105
Ensembl biotype	protein_coding
Entrez	399671

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 5 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000334988, ENST00000553558, ENST00000556455, ENST00000557603, ENST00000563329, ENST00000565094, ENST00000566478

RefSeq mRNA: 2 — MANE Select: NM_001220484 NM_001220484, NM_203309

CCDS: CCDS9815

Canonical transcript exons

ENST00000553558 — 18 exons

Exon	Start	End
ENSE00001331685	73493066	73493124
ENSE00001331690	73495228	73495387
ENSE00001331694	73496601	73496679
ENSE00001331697	73498155	73498344
ENSE00001331701	73499071	73499140
ENSE00001331705	73500550	73500730
ENSE00001331709	73502895	73503013
ENSE00001331713	73506467	73506571
ENSE00001331717	73508134	73508294
ENSE00001331720	73509312	73509473
ENSE00001331723	73512006	73512149
ENSE00001331724	73514031	73514234
ENSE00001331730	73519023	73519163
ENSE00001331733	73520852	73521039
ENSE00001331738	73522272	73523224
ENSE00002451289	73530166	73530244
ENSE00002475887	73478484	73478842
ENSE00003902056	73558751	73558947

Expression profiles

Bgee: expression breadth ubiquitous, 162 present calls, max score 82.00.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0097 / max 7.2174, expressed in 3 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
143971	0.0097	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right testis	UBERON:0004534	82.00	gold quality
left testis	UBERON:0004533	81.44	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.03	gold quality
testis	UBERON:0000473	79.00	gold quality
cerebellar hemisphere	UBERON:0002245	76.48	gold quality
cerebellar cortex	UBERON:0002129	76.39	gold quality
right hemisphere of cerebellum	UBERON:0014890	75.38	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	75.30	gold quality
cerebellum	UBERON:0002037	75.22	gold quality
sperm	CL:0000019	74.82	gold quality
right lobe of liver	UBERON:0001114	74.66	gold quality
nucleus accumbens	UBERON:0001882	69.64	gold quality
Brodmann (1909) area 9	UBERON:0013540	68.96	gold quality
putamen	UBERON:0001874	68.67	gold quality
right frontal lobe	UBERON:0002810	68.26	gold quality
anterior cingulate cortex	UBERON:0009835	67.80	gold quality
mucosa of transverse colon	UBERON:0004991	67.76	gold quality
caudate nucleus	UBERON:0001873	67.75	gold quality
amygdala	UBERON:0001876	67.39	gold quality
cortical plate	UBERON:0005343	67.33	gold quality
gastrocnemius	UBERON:0001388	67.10	gold quality
muscle of leg	UBERON:0001383	66.84	gold quality
calcaneal tendon	UBERON:0003701	66.72	gold quality
tibial nerve	UBERON:0001323	66.18	gold quality
rectum	UBERON:0001052	65.91	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	65.46	gold quality
small intestine Peyer’s patch	UBERON:0003454	65.45	gold quality
apex of heart	UBERON:0002098	65.14	gold quality
primary visual cortex	UBERON:0002436	65.13	gold quality
hypothalamus	UBERON:0001898	65.07	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.08

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

15 targeting HEATR4, 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-5692A	100.00	74.40	6850
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-LET-7A-2-3P	99.87	70.53	1921
HSA-LET-7G-3P	99.85	70.43	1929
HSA-MIR-516A-3P	99.46	67.96	1378
HSA-MIR-516B-3P	99.46	67.96	1378
HSA-MIR-7162-5P	99.46	68.08	1368
HSA-MIR-324-3P	99.26	66.31	1034
HSA-MIR-4504	99.10	69.14	1328
HSA-MIR-4635	98.74	67.63	1339
HSA-MIR-508-3P	98.66	69.62	887
HSA-MIR-4275	97.96	68.42	1549
HSA-MIR-3667-5P	97.16	64.87	591

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	heatr4	ENSDARG00000090753
mus_musculus	Heatr4	ENSMUSG00000090843
rattus_norvegicus	Heatr4	ENSRNOG00000038183

Protein

Protein identifiers

HEAT repeat-containing protein 4 — Q86WZ0 (reviewed: Q86WZ0)

All UniProt accessions (4): G3V3Q5, G3V5L2, H3BSP2, Q86WZ0

UniProt curated annotations — full annotation on UniProt →

RefSeq proteins (2): NP_001207413, NP_976054 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000357	HEAT	Repeat
IPR011989	ARM-like	Homologous_superfamily
IPR016024	ARM-type_fold	Homologous_superfamily

Pfam: PF02985, PF13646

UniProt features (8 total): repeat 3, sequence variant 3, chain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86WZ0-F1	65.73	0.22

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 11 (showing top): chr14q24, APPIERTO_RESPONSE_TO_FENRETINIDE_DN, CAMPS_COLON_CANCER_COPY_NUMBER_DN, RFX1_01, MIR4753_3P, MIR4635, MIR3667_5P, GOMF_OXIDOREDUCTASE_ACTIVITY, GSE17974_IL4_AND_ANTI_IL12_VS_UNTREATED_1H_ACT_CD4_TCELL_UP, GSE29617_CTRL_VS_DAY7_TIV_FLU_VACCINE_PBMC_2008_UP, GSE43863_NAIVE_VS_MEMORY_TH1_CD4_TCELL_D150_LCMV_DN

GO Biological Process (0):

GO Molecular Function (2): oxidoreductase activity (GO:0016491), protein binding (GO:0005515)

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
catalytic activity	1
binding	1

Protein interactions and networks

STRING

322 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HEATR4	ACOT1	Q86TX2	588
HEATR4	ACOT2	P49753	552
HEATR4	RPS6KL1	Q9Y6S9	496
HEATR4	INTS4	Q96HW7	491
HEATR4	DEPDC4	Q8N2C3	487
HEATR4	RSPH14	Q9UHP6	482
HEATR4	LRRC61	Q9BV99	447
HEATR4	HEATR6	Q6AI08	446
HEATR4	TNFRSF10D	Q9UBN6	444
HEATR4	STK36	Q9NRP7	439
HEATR4	PROX2	Q3B8N5	436
HEATR4	MROH7	Q68CQ1	433
HEATR4	RIOX1	Q9H6W3	430
HEATR4	AREL1	O15033	429
HEATR4	ACOT4	Q8N9L9	428

IntAct

3 interactions, top by confidence:

A	B	Type	Score
HEATR4	HSPA9	psi-mi:“MI:0915”(physical association)	0.400
ESR2		psi-mi:“MI:0914”(association)	0.350

BioGRID (2): HEATR4 (Affinity Capture-MS), HEATR4 (Proximity Label-MS)

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

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	31
Likely benign	5
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

4386 predictions. Top by Δscore:

Variant	Effect	Δscore
14:73496675:TTTCT:T	acceptor_gain	1.0000
14:73498153:A:AC	donor_gain	1.0000
14:73498154:C:CA	donor_gain	1.0000
14:73498154:CT:C	donor_gain	1.0000
14:73498156:TTAGA:T	donor_gain	1.0000
14:73498340:CAAAG:C	acceptor_gain	1.0000
14:73498341:AAAG:A	acceptor_gain	1.0000
14:73498342:AAG:A	acceptor_gain	1.0000
14:73498343:AG:A	acceptor_gain	1.0000
14:73498345:C:CC	acceptor_gain	1.0000
14:73498346:T:G	acceptor_loss	1.0000
14:73506391:G:C	donor_gain	1.0000
14:73508132:A:AC	donor_gain	1.0000
14:73508133:C:CC	donor_gain	1.0000
14:73509308:TCA:T	donor_loss	1.0000
14:73509309:CACCC:C	donor_loss	1.0000
14:73509310:A:AC	donor_gain	1.0000
14:73509310:AC:A	donor_gain	1.0000
14:73509310:ACCCT:A	donor_loss	1.0000
14:73509311:C:A	donor_loss	1.0000
14:73509311:C:CC	donor_gain	1.0000
14:73509311:CC:C	donor_gain	1.0000
14:73509469:CTTGT:C	acceptor_gain	1.0000
14:73509470:TTGT:T	acceptor_gain	1.0000
14:73509472:GT:G	acceptor_gain	1.0000
14:73509474:C:CC	acceptor_gain	1.0000
14:73509474:CTGT:C	acceptor_loss	1.0000
14:73509481:C:CT	acceptor_gain	1.0000
14:73512000:TCTCA:T	donor_loss	1.0000
14:73512001:CTCA:C	donor_loss	1.0000

AlphaMissense

6712 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:73498241:G:C	S820R	0.982
14:73498241:G:T	S820R	0.982
14:73498243:T:G	S820R	0.982
14:73498252:C:G	A817P	0.982
14:73514205:A:G	W414R	0.978
14:73514205:A:T	W414R	0.978
14:73502949:G:T	A684D	0.977
14:73509387:C:G	A549P	0.976
14:73512141:A:G	W475R	0.976
14:73512141:A:T	W475R	0.976
14:73514052:A:G	W465R	0.975
14:73514052:A:T	W465R	0.975
14:73500588:A:G	C750R	0.973
14:73512116:A:G	L483P	0.970
14:73500578:G:T	A753D	0.969
14:73509384:C:G	A550P	0.969
14:73499079:G:T	A783D	0.966
14:73502950:C:G	A684P	0.966
14:73522934:G:C	F73L	0.966
14:73522934:G:T	F73L	0.966
14:73522936:A:G	F73L	0.966
14:73500590:G:T	A749D	0.965
14:73506516:C:G	R646P	0.965
14:73514203:C:A	W414C	0.965
14:73514203:C:G	W414C	0.965
14:73498260:C:G	R814P	0.963
14:73508268:C:G	A583P	0.962
14:73500647:A:G	L730P	0.961
14:73506540:A:G	L638P	0.961
14:73508271:C:G	A582P	0.961

dbSNP variants (sampled 300 via entrez): RS1000028636 (14:73517976 C>T), RS1000042399 (14:73496632 T>C), RS1000117038 (14:73602837 C>T), RS1000119696 (14:73631579 C>T), RS1000121234 (14:73478982 A>G,T), RS1000135040 (14:73524860 A>G), RS1000172637 (14:73590448 A>C,G), RS1000184455 (14:73601479 G>A), RS1000190326 (14:73543268 G>A), RS1000195210 (14:73631324 C>G), RS1000236440 (14:73591535 C>T), RS1000236951 (14:73602606 C>T), RS1000241455 (14:73485234 A>G), RS1000258741 (14:73634168 G>A), RS1000273386 (14:73596575 T>C)

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

3 associations (top):

Study	Trait	p-value
GCST008745_4	Estimated glomerular filtration rate in non-diabetics	4.000000e-08
GCST010083_268	Hemoglobin levels	9.000000e-14
GCST90002402_191	Platelet count	2.000000e-10

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004509	hemoglobin measurement
EFO:0004309	platelet count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs147204125	ACOT6, HEATR4		0.00	0
rs758109	ACOT1, HEATR4, RIOX1		0.00	0

CTD chemical–gene interactions

14 total (human), top 14 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Resveratrol	affects cotreatment, decreases expression	2
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	2
Aflatoxin B1	decreases methylation, increases methylation	2
aristolochic acid I	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, increases methylation	1
abrine	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Arsenic	affects methylation	1
Copper	affects cotreatment, decreases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1

Clinical trials (associated diseases)

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