HEATR5A

Summary

HEATR5A (HEAT repeat containing 5A, HGNC:20276) is a protein-coding gene on chromosome 14q12, encoding HEAT repeat-containing protein 5A (Q86XA9).

Predicted to be involved in endocytosis; protein localization; and retrograde transport, endosome to Golgi. Predicted to be located in cytosol. Predicted to be active in endocytic vesicle.

Source: NCBI Gene 25938 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 355 total
• MANE Select transcript: NM_015473

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20276
Approved symbol	HEATR5A
Name	HEAT repeat containing 5A
Location	14q12
Locus type	gene with protein product
Status	Approved
Aliases	DKFZP434I1735, p200b
Ensembl gene	ENSG00000129493
Ensembl biotype	protein_coding
Entrez	25938

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 17 protein_coding, 2 retained_intron

ENST00000382464, ENST00000538864, ENST00000543095, ENST00000549184, ENST00000549719, ENST00000550366, ENST00000550819, ENST00000551414, ENST00000552500, ENST00000892404, ENST00000892405, ENST00000892406, ENST00000892407, ENST00000892408, ENST00000925433, ENST00000925434, ENST00000925435, ENST00000925436, ENST00000925437

RefSeq mRNA: 1 — MANE Select: NM_015473 NM_015473

CCDS: CCDS45094

Canonical transcript exons

ENST00000543095 — 36 exons

Exon	Start	End
ENSE00000940435	31318224	31318292
ENSE00000940436	31315770	31315949
ENSE00000940437	31312968	31313190
ENSE00000940440	31306732	31306879
ENSE00001170348	31295909	31296063
ENSE00001170354	31302295	31302519
ENSE00001170361	31304905	31305177
ENSE00001170370	31307893	31308020
ENSE00001170380	31308934	31309182
ENSE00001170404	31321499	31321680
ENSE00001507350	31323565	31323804
ENSE00001507351	31326163	31326342
ENSE00002346980	31420472	31420550
ENSE00002394301	31291788	31293612
ENSE00003465642	31398673	31398781
ENSE00003472021	31343896	31344065
ENSE00003474994	31402850	31403049
ENSE00003479636	31350612	31350717
ENSE00003505536	31374816	31374968
ENSE00003508414	31380467	31380578
ENSE00003521101	31386420	31386575
ENSE00003525966	31371810	31371909
ENSE00003538710	31394052	31394226
ENSE00003557768	31345087	31345276
ENSE00003565837	31358637	31358812
ENSE00003574959	31395199	31395348
ENSE00003580336	31400301	31400512
ENSE00003588574	31337476	31337614
ENSE00003590103	31388845	31389005
ENSE00003595269	31347748	31347907
ENSE00003597334	31364189	31364298
ENSE00003620134	31383521	31383771
ENSE00003628641	31387120	31387375
ENSE00003629331	31349789	31349979
ENSE00003639872	31358894	31359057
ENSE00003681523	31293891	31294104

Expression profiles

Bgee: expression breadth ubiquitous, 251 present calls, max score 93.88.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 20.6329 / max 416.8422, expressed in 1816 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
142740	19.2712	1814
142741	1.2924	948
142739	0.0383	10
142738	0.0311	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	93.88	gold quality
ileal mucosa	UBERON:0000331	93.52	gold quality
left ventricle myocardium	UBERON:0006566	92.92	gold quality
adrenal tissue	UBERON:0018303	92.80	gold quality
cardiac muscle of right atrium	UBERON:0003379	91.06	gold quality
corpus callosum	UBERON:0002336	90.91	gold quality
calcaneal tendon	UBERON:0003701	89.54	gold quality
stromal cell of endometrium	CL:0002255	88.96	gold quality
tibialis anterior	UBERON:0001385	88.64	gold quality
jejunal mucosa	UBERON:0000399	88.46	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.62	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.61	gold quality
oviduct epithelium	UBERON:0004804	86.97	gold quality
heart right ventricle	UBERON:0002080	86.82	gold quality
epithelial cell of pancreas	CL:0000083	86.74	silver quality
islet of Langerhans	UBERON:0000006	86.44	gold quality
deltoid	UBERON:0001476	86.22	silver quality
placenta	UBERON:0001987	85.95	gold quality
colonic mucosa	UBERON:0000317	85.53	gold quality
myocardium	UBERON:0002349	85.43	gold quality
bronchial epithelial cell	CL:0002328	85.39	gold quality
monocyte	CL:0000576	85.25	gold quality
heart left ventricle	UBERON:0002084	85.09	gold quality
cardiac ventricle	UBERON:0002082	85.00	gold quality
leukocyte	CL:0000738	84.77	gold quality
bronchus	UBERON:0002185	84.68	gold quality
mucosa of sigmoid colon	UBERON:0004993	84.67	gold quality
tibia	UBERON:0000979	84.40	gold quality
endothelial cell	CL:0000115	84.35	silver quality
adrenal gland	UBERON:0002369	84.26	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.64
E-CURD-112	no	2.76

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

95 targeting HEATR5A, 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-3163	100.00	77.23	8605
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-3617-3P	99.98	67.86	918
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-130A-3P	99.90	73.31	1861
HSA-MIR-130B-3P	99.90	73.27	1850
HSA-MIR-301A-3P	99.90	73.15	1839
HSA-MIR-301B-3P	99.90	73.19	1836
HSA-MIR-3666	99.90	73.24	1833
HSA-MIR-4295	99.90	73.11	1838

Literature-anchored findings (GeneRIF, showing 1)

• Fast-evolving cofactors regulate the role of HEATR5 complexes in intra-Golgi trafficking. (PMID:38240799)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	heatr5a	ENSDARG00000023999
mus_musculus	Heatr5a	ENSMUSG00000035181
rattus_norvegicus	Heatr5a	ENSRNOG00000006483
drosophila_melanogaster	CG2747	FBGN0037541
caenorhabditis_elegans		WBGENE00015743

Paralogs (1): HEATR5B (ENSG00000008869)

Protein

Protein identifiers

HEAT repeat-containing protein 5A — Q86XA9 (reviewed: Q86XA9)

All UniProt accessions (7): Q86XA9, F5H619, F8VQQ6, H0YHE0, H0YHS5, H0YIW3, H7C5W6

UniProt curated annotations — full annotation on UniProt →

Similarity. Belongs to the HEATR5 family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q86XA9-1	1	yes
Q86XA9-2	2
Q86XA9-3	3

RefSeq proteins (1): NP_056288* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011989	ARM-like	Homologous_superfamily
IPR016024	ARM-type_fold	Homologous_superfamily
IPR040108	Laa1/Sip1/HEATR5	Family
IPR046837	Laa1/Sip1/HEATR5-like_HEAT	Repeat

Pfam: PF20210, PF25468

UniProt features (14 total): sequence conflict 5, modified residue 3, repeat 2, splice variant 2, chain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86XA9-F1	81.42	0.33

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (3): 1110, 1115, 1647

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 107 (showing top): MODULE_169, GOBP_VESICLE_MEDIATED_TRANSPORT, chr14q12, GOBP_RETROGRADE_TRANSPORT_ENDOSOME_TO_GOLGI, CUI_TCF21_TARGETS_2_DN, RICKMAN_TUMOR_DIFFERENTIATED_MODERATELY_VS_POORLY_UP, GOBP_IMPORT_INTO_CELL, ACEVEDO_METHYLATED_IN_LIVER_CANCER_DN, GOBP_ENDOCYTOSIS, GOBP_CYTOSOLIC_TRANSPORT, GOCC_ENDOCYTIC_VESICLE, ZHENG_BOUND_BY_FOXP3, ZHENG_FOXP3_TARGETS_IN_THYMUS_UP, TAKEDA_TARGETS_OF_NUP98_HOXA9_FUSION_6HR_UP, GOBP_ENDOSOMAL_TRANSPORT

GO Biological Process (3): endocytosis (GO:0006897), intracellular protein localization (GO:0008104), retrograde transport, endosome to Golgi (GO:0042147)

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

GO Cellular Component (3): Golgi apparatus (GO:0005794), cytosol (GO:0005829), endocytic vesicle (GO:0030139)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	2
vesicle budding from membrane	1
membrane invagination	1
vesicle-mediated transport	1
import into cell	1
macromolecule localization	1
intercellular transport	1
endosomal transport	1
cytosolic transport	1
binding	1
endomembrane system	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1
cytoplasmic vesicle	1

Protein interactions and networks

STRING

560 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HEATR5A	DTD2	Q96FN9	591
HEATR5A	GPR33	Q49SQ1	478
HEATR5A	IQCJ	Q1A5X6	462
HEATR5A	FAM170B	A6NMN3	447
HEATR5A	IQCB1	Q15051	443
HEATR5A	CWF19L2	Q2TBE0	413
HEATR5A	FAM186A	A6NE01	368
HEATR5A	ARHGEF1	Q92888	357
HEATR5A	SCFD1	Q8WVM8	353
HEATR5A	TNS1	Q9HBL0	352
HEATR5A	PRAMEF12	O95522	349
HEATR5A	NUBPL	Q8TB37	348
HEATR5A	ARHGEF37	A1IGU5	348
HEATR5A	AP3B2	Q13367	337
HEATR5A	LUZP2	Q86TE4	330

IntAct

19 interactions, top by confidence:

A	B	Type	Score
ANKRD22	ESYT2	psi-mi:“MI:0914”(association)	0.530
	TK2	psi-mi:“MI:0915”(physical association)	0.400
HEATR5A	CFTR	psi-mi:“MI:0915”(physical association)	0.370
CSDE1	PABPC4L	psi-mi:“MI:0914”(association)	0.350
SCOC	SSNA1	psi-mi:“MI:0914”(association)	0.350
PPM1B	BPGM	psi-mi:“MI:0914”(association)	0.350
KIF6	ACADS	psi-mi:“MI:0914”(association)	0.350
PA	ESYT2	psi-mi:“MI:0914”(association)	0.350
GPR17	TMEM120B	psi-mi:“MI:0914”(association)	0.350
DLL1	GNPAT	psi-mi:“MI:0914”(association)	0.350
SCOC	SNAPIN	psi-mi:“MI:0914”(association)	0.350
TTI1	HERC1	psi-mi:“MI:0914”(association)	0.350
AFG2B	MMP24OS	psi-mi:“MI:0914”(association)	0.350
PPM1B		psi-mi:“MI:0914”(association)	0.350
S1PR3	STXBP3	psi-mi:“MI:0914”(association)	0.350

BioGRID (31): HEATR5A (Affinity Capture-MS), PPIA (Co-fractionation), HEATR5A (Affinity Capture-MS), HEATR5A (Affinity Capture-MS), HEATR5A (Affinity Capture-MS), HEATR5A (Affinity Capture-MS), HEATR5A (Affinity Capture-RNA), WDYHV1 (Two-hybrid), HEATR5A (Affinity Capture-MS), HEATR5A (Affinity Capture-MS), HEATR5A (Affinity Capture-MS), HEATR5A (Proximity Label-MS), HEATR5A (Proximity Label-MS), HEATR5A (Proximity Label-MS), HEATR5A (Affinity Capture-MS)

ESM2 similar proteins: A0JP94, A1A5F2, A1EC95, A2BID5, A9JRI0, E7FAW3, E7FBU4, E9PVA8, F4HRS2, F4IP13, K8ERU3, O35095, O43299, P42695, P49815, P49816, Q08CY4, Q0DJS1, Q28205, Q2KJ97, Q3U829, Q3UHQ6, Q5JWR5, Q5PRF0, Q5R5R2, Q5SPP5, Q5ZIG0, Q61037, Q640K1, Q642P2, Q68F70, Q6AI08, Q6GN08, Q6GPP1, Q6P1G0, Q6ZNJ1, Q6ZQA0, Q6ZQK0, Q7T006, Q7ZY56

Diamond homologs: A0JP94, A1A5F2, Q5PRF0, Q86XA9, Q8C547, Q8JFV4, Q9P2D3, P39526

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	310
Likely benign	8
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

7057 predictions. Top by Δscore:

Variant	Effect	Δscore
14:31293884:CA:C	donor_gain	1.0000
14:31293889:A:AC	donor_gain	1.0000
14:31293890:C:CT	donor_gain	1.0000
14:31293890:CG:C	donor_gain	1.0000
14:31293890:CGAT:C	donor_gain	1.0000
14:31293890:CGATG:C	donor_gain	1.0000
14:31294104:CC:C	acceptor_loss	1.0000
14:31294106:T:A	acceptor_loss	1.0000
14:31295907:A:AC	donor_gain	1.0000
14:31295908:C:CC	donor_gain	1.0000
14:31295908:CCA:C	donor_gain	1.0000
14:31295991:C:CC	acceptor_gain	1.0000
14:31296064:C:CC	acceptor_gain	1.0000
14:31305101:T:A	donor_gain	1.0000
14:31306811:C:CC	acceptor_gain	1.0000
14:31307892:CCTGA:C	donor_gain	1.0000
14:31307972:T:A	donor_gain	1.0000
14:31321493:GCTTA:G	donor_loss	1.0000
14:31321494:CTTA:C	donor_loss	1.0000
14:31321495:TTA:T	donor_loss	1.0000
14:31321496:TAC:T	donor_loss	1.0000
14:31321497:A:AC	donor_gain	1.0000
14:31321498:C:CA	donor_gain	1.0000
14:31321498:C:G	donor_loss	1.0000
14:31321498:CA:C	donor_gain	1.0000
14:31321498:CAT:C	donor_gain	1.0000
14:31321498:CATT:C	donor_gain	1.0000
14:31321498:CATTG:C	donor_gain	1.0000
14:31321681:C:CC	acceptor_gain	1.0000
14:31321698:A:C	acceptor_gain	1.0000

AlphaMissense

13174 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000004204 (14:31390146 C>T), RS1000010828 (14:31305317 C>T), RS1000034357 (14:31396427 G>A,C), RS1000045138 (14:31354930 T>A), RS1000071081 (14:31304180 G>A), RS1000119940 (14:31390368 A>G), RS1000120503 (14:31311831 G>A,C), RS1000125669 (14:31409344 G>A), RS1000141297 (14:31354606 T>A,C), RS1000206275 (14:31415921 A>G), RS1000229912 (14:31371668 G>A), RS1000266702 (14:31367052 A>G), RS1000272595 (14:31409489 G>A), RS1000281469 (14:31329392 G>C), RS1000320680 (14:31292714 C>G)

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

2 associations (top):

Study	Trait	p-value
GCST008362_53	Birth weight	4.000000e-08
GCST008810_52	Smoking initiation (ever regular vs never regular)	1.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004344	birth weight
EFO:0005670	smoking initiation

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

41 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression	4
sodium arsenite	decreases expression	2
methacrylaldehyde	increases abundance, affects cotreatment, increases oxidation, decreases expression	2
epigallocatechin gallate	decreases expression, affects cotreatment	2
Acrolein	affects cotreatment, increases oxidation, decreases expression, increases abundance	2
Air Pollutants	decreases expression, affects cotreatment, increases abundance, increases oxidation	2
Ozone	affects cotreatment, increases oxidation, decreases expression, increases abundance	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression, increases expression	2
GSK-J4	increases expression	1
FR900359	decreases phosphorylation	1
triphenyl phosphate	affects expression	1
alpha-pinene	increases abundance, affects cotreatment, increases oxidation	1
bisphenol A	decreases expression	1
decabromobiphenyl ether	decreases expression	1
tetrabromobisphenol A	decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
corosolic acid	increases expression	1
2-palmitoylglycerol	increases expression	1
monomethylarsonous acid	increases expression	1
abrine	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
NSC 689534	increases expression, affects binding	1
(+)-JQ1 compound	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Leflunomide	decreases expression	1
Acetaminophen	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Copper	affects binding, increases expression	1
Diethylhexyl Phthalate	increases expression	1

Clinical trials (associated diseases)

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