PHYHIP

Summary

PHYHIP (phytanoyl-CoA 2-hydroxylase interacting protein, HGNC:16865) is a protein-coding gene on chromosome 8p21.3, encoding Phytanoyl-CoA hydroxylase-interacting protein (Q92561). Its interaction with PHYH suggests a role in the development of the central system.

Enables protein tyrosine kinase binding activity. Involved in protein localization. Located in cytoplasm.

Source: NCBI Gene 9796 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 23 total
• MANE Select transcript: NM_014759

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16865
Approved symbol	PHYHIP
Name	phytanoyl-CoA 2-hydroxylase interacting protein
Location	8p21.3
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0273, PAHX-AP
Ensembl gene	ENSG00000168490
Ensembl biotype	protein_coding
OMIM	608511
Entrez	9796

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 7 protein_coding, 2 retained_intron

ENST00000321613, ENST00000454243, ENST00000518274, ENST00000522869, ENST00000523252, ENST00000934692, ENST00000934693, ENST00000934694, ENST00000954726

RefSeq mRNA: 4 — MANE Select: NM_014759 NM_001099335, NM_001363311, NM_001363312, NM_014759

CCDS: CCDS43723

Canonical transcript exons

ENST00000454243 — 5 exons

Exon	Start	End
ENSE00001159253	22224226	22224343
ENSE00001223358	22228193	22228386
ENSE00001359193	22231796	22232099
ENSE00002130467	22219703	22221887
ENSE00003479091	22226851	22227025

Expression profiles

Bgee: expression breadth ubiquitous, 207 present calls, max score 99.39.

FANTOM5 (CAGE): breadth broad, TPM avg 21.6935 / max 1388.4403, expressed in 406 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
92220	19.3312	390
92219	0.4874	86
92225	0.4825	77
92222	0.3938	85
92218	0.3501	82
92221	0.2422	80
92217	0.2045	65
92226	0.0812	46
92223	0.0671	39
92224	0.0536	40

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	99.39	gold quality
cerebellar hemisphere	UBERON:0002245	99.36	gold quality
cerebellar cortex	UBERON:0002129	99.35	gold quality
cerebellum	UBERON:0002037	99.08	gold quality
middle frontal gyrus	UBERON:0002702	99.04	gold quality
Brodmann (1909) area 10	UBERON:0013541	99.03	gold quality
paraflocculus	UBERON:0005351	98.89	gold quality
right frontal lobe	UBERON:0002810	98.87	gold quality
Brodmann (1909) area 9	UBERON:0013540	98.53	gold quality
nucleus accumbens	UBERON:0001882	98.48	gold quality
prefrontal cortex	UBERON:0000451	98.42	gold quality
putamen	UBERON:0001874	98.24	gold quality
caudate nucleus	UBERON:0001873	98.21	gold quality
frontal cortex	UBERON:0001870	98.06	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	98.03	gold quality
frontal pole	UBERON:0002795	98.01	gold quality
primary visual cortex	UBERON:0002436	97.93	gold quality
cingulate cortex	UBERON:0003027	97.85	gold quality
anterior cingulate cortex	UBERON:0009835	97.85	gold quality
neocortex	UBERON:0001950	97.40	gold quality
middle temporal gyrus	UBERON:0002771	97.30	gold quality
superior frontal gyrus	UBERON:0002661	97.29	gold quality
cerebellar vermis	UBERON:0004720	97.22	gold quality
amygdala	UBERON:0001876	96.89	gold quality
occipital lobe	UBERON:0002021	96.89	gold quality
cerebral cortex	UBERON:0000956	96.88	gold quality
telencephalon	UBERON:0001893	96.83	gold quality
Ammon’s horn	UBERON:0001954	96.24	gold quality
temporal lobe	UBERON:0001871	96.15	gold quality
parietal lobe	UBERON:0001872	96.14	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-HCAD-35	yes	40.84
E-ANND-3	yes	4.96

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

66 targeting PHYHIP, 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-4481	100.00	66.42	1669
HSA-MIR-6798-5P	100.00	65.77	699
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-4648	99.91	67.00	710
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-6817-3P	99.79	68.35	2126
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-2116-3P	99.74	64.32	889
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-1296-3P	99.72	64.04	636
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-6797-5P	99.61	66.55	2084
HSA-MIR-1249-5P	99.61	66.55	2049
HSA-MIR-4516	99.61	67.78	3390

Literature-anchored findings (GeneRIF, showing 2)

• PAHX-AP1 may contribute to new cellular functions of DYRK1A and suggest that PAHX-AP1 may be involved in the development of neurological abnormalities observed in Down syndrome patients (PMID:15694837)
• High placental expression of FLT1, LEP, PHYHIP and IL3RA - In persons of African ancestry with severe preeclampsia. (PMID:37949031)

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
danio_rerio	phyhip	ENSDARG00000116497
mus_musculus	Phyhip	ENSMUSG00000003469
rattus_norvegicus	Phyhip	ENSRNOG00000010555
caenorhabditis_elegans		WBGENE00010803
caenorhabditis_elegans		WBGENE00011697
caenorhabditis_elegans	Y92H12BR.7	WBGENE00022372
caenorhabditis_elegans		WBGENE00045337
caenorhabditis_elegans		WBGENE00045338
caenorhabditis_elegans		WBGENE00045339

Paralogs (1): PHYHIPL (ENSG00000165443)

Protein

Protein identifiers

Phytanoyl-CoA hydroxylase-interacting protein — Q92561 (reviewed: Q92561)

Alternative names: Phytanoyl-CoA hydroxylase-associated protein 1

All UniProt accessions (2): E5RHN5, Q92561

UniProt curated annotations — full annotation on UniProt →

Function. Its interaction with PHYH suggests a role in the development of the central system.

Subunit / interactions. Interacts with PHYH and ADGRB1.

Tissue specificity. Highly expressed in the brain.

Similarity. Belongs to the PHYHIP family.

RefSeq proteins (4): NP_001092805, NP_001350240, NP_001350241, NP_055574* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003961	FN3_dom	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR036116	FN3_sf	Homologous_superfamily
IPR042868	PHYHIP/PHYHIPL	Family
IPR045545	PHYIP/PHIPL_C	Domain

Pfam: PF19281

UniProt features (8 total): sequence conflict 3, glycosylation site 2, chain 1, domain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q92561-F1	89.99	0.73

Functional residue map

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

Glycosylation sites (2): 14, 325

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 114 (showing top): GGGTGGRR_PAX4_03, MODULE_66, chr8p21, AAACCAC_MIR140, MODULE_256, GNF2_TM4SF2, VANHARANTA_UTERINE_FIBROID_DN, PPAR_DR1_Q2, MODULE_88, AACTTT_UNKNOWN, GFI1_01, HAND1E47_01, PTF1BETA_Q6, MODULE_11, MODULE_95

GO Biological Process (1): intracellular protein localization (GO:0008104)

GO Molecular Function (2): protein tyrosine kinase binding (GO:1990782), protein binding (GO:0005515)

GO Cellular Component (1): cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
macromolecule localization	1
protein kinase binding	1
binding	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1396 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PHYHIP	PHYH	O14832	986
PHYHIP	ADGRB1	O14514	523
PHYHIP	LENG9	Q96B70	417
PHYHIP	LGI3	Q8N145	400
PHYHIP	MED8	Q96G25	381
PHYHIP	GJD4	Q96KN9	358
PHYHIP	TMEM64	Q6YI46	353
PHYHIP	RETSAT	Q6NUM9	351
PHYHIP	ILRUN	Q9H6K1	335
PHYHIP	CPNE6	O95741	334
PHYHIP	RASL11A	Q6T310	333
PHYHIP	FAM78A	Q5JUQ0	326
PHYHIP	SLC26A10P	Q8NG04	323
PHYHIP	TCF23	Q7RTU1	322
PHYHIP	FBXL16	Q8N461	321

IntAct

37 interactions, top by confidence:

A	B	Type	Score
CA10	WDHD1	psi-mi:“MI:0914”(association)	0.640
PAQR5	PHYHIP	psi-mi:“MI:0915”(physical association)	0.590
PHYHIP	TRIP6	psi-mi:“MI:0914”(association)	0.530
TMEM255B	PHYHIP	psi-mi:“MI:0914”(association)	0.530
ANKRD12	SLIT2	psi-mi:“MI:0914”(association)	0.350
MSI2	ANXA13	psi-mi:“MI:0914”(association)	0.350
PARL	CCDC92	psi-mi:“MI:0914”(association)	0.350
TMEM255B	PLXDC2	psi-mi:“MI:0914”(association)	0.350
COG7	TRAF5	psi-mi:“MI:0914”(association)	0.350
PHYHIP	ERG28	psi-mi:“MI:0915”(physical association)	0.000
PHYHIP	COPS6	psi-mi:“MI:0915”(physical association)	0.000
PHYHIP	EEF1A1	psi-mi:“MI:0915”(physical association)	0.000
PHYHIP	MED8	psi-mi:“MI:0915”(physical association)	0.000
PHYHIP	NDRG1	psi-mi:“MI:0915”(physical association)	0.000
PHYHIP	TTR	psi-mi:“MI:0915”(physical association)	0.000
PHYHIP	PNPLA2	psi-mi:“MI:0915”(physical association)	0.000
SUPT5H	PHYHIP	psi-mi:“MI:0915”(physical association)	0.000
PHYHIP	HDAC11	psi-mi:“MI:0915”(physical association)	0.000
PHYHIP	WDR89	psi-mi:“MI:0915”(physical association)	0.000
PHYHIP	MAGED4B	psi-mi:“MI:0915”(physical association)	0.000
PHYHIP	FAM131A	psi-mi:“MI:0915”(physical association)	0.000
PHYHIP	METTL18	psi-mi:“MI:0915”(physical association)	0.000
PHYHIP	NDUFV3	psi-mi:“MI:0915”(physical association)	0.000
PHYHIP	PPIE	psi-mi:“MI:0915”(physical association)	0.000
PHYHIP	S100A13	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (55): PHYHIP (Affinity Capture-MS), PHYHIP (Affinity Capture-MS), PHYHIP (Affinity Capture-MS), KIF15 (Affinity Capture-MS), PTRH2 (Affinity Capture-MS), PRKD2 (Affinity Capture-MS), LIMD1 (Affinity Capture-MS), TRIP6 (Affinity Capture-MS), PHYHIP (Affinity Capture-MS), KIF15 (Affinity Capture-MS), PHYHIP (Affinity Capture-MS), LIMD1 (Affinity Capture-MS), PRKD2 (Affinity Capture-MS), PHYHIP (Affinity Capture-MS), PHYHIP (Affinity Capture-MS)

ESM2 similar proteins: A0A2B4RNI3, A0A3M6TIF0, A0A8B8EY61, A0A913XCT1, A6NKT7, B1WBT0, G5ED39, H2QII6, O14715, O36371, O36385, O36386, O36406, P0DJD0, P0DJD1, P24447, P32742, P33802, P34335, P42286, P49792, P52344, P52448, P90245, Q01013, Q01015, Q0VD34, Q13535, Q18LD0, Q23652, Q499E0, Q568Z9, Q5PQN2, Q5R4I8, Q5RBY8, Q6ZN28, Q751Y8, Q76B58, Q7Z3J3, Q8K0S0

Diamond homologs: A4QNW7, Q0V9U8, Q0VD34, Q32L96, Q568Z9, Q5R4I8, Q6AX58, Q6AYN4, Q8BGT8, Q8K0S0, Q92561, Q96FC7

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	21
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

850 predictions. Top by Δscore:

Variant	Effect	Δscore
8:22221898:C:CT	acceptor_gain	1.0000
8:22221899:A:T	acceptor_gain	1.0000
8:22221908:C:CT	acceptor_gain	1.0000
8:22221911:C:CT	acceptor_gain	1.0000
8:22221911:C:T	acceptor_gain	1.0000
8:22221912:A:T	acceptor_gain	1.0000
8:22224220:CCATA:C	donor_loss	1.0000
8:22224223:TACCT:T	donor_loss	1.0000
8:22224224:ACCTG:A	donor_loss	1.0000
8:22224225:C:CG	donor_loss	1.0000
8:22224245:C:CA	donor_gain	1.0000
8:22224340:TAAT:T	acceptor_gain	1.0000
8:22224341:AATC:A	acceptor_loss	1.0000
8:22224342:AT:A	acceptor_gain	1.0000
8:22224343:TC:T	acceptor_loss	1.0000
8:22224344:C:CC	acceptor_gain	1.0000
8:22224344:C:CG	acceptor_loss	1.0000
8:22226846:CTCAC:C	donor_loss	1.0000
8:22226847:TCA:T	donor_loss	1.0000
8:22226849:A:T	donor_loss	1.0000
8:22226849:AC:A	donor_gain	1.0000
8:22226849:ACC:A	donor_gain	1.0000
8:22226849:ACCC:A	donor_gain	1.0000
8:22226850:CC:C	donor_gain	1.0000
8:22226850:CCC:C	donor_gain	1.0000
8:22226850:CCCC:C	donor_gain	1.0000
8:22226899:C:CA	donor_gain	1.0000
8:22226900:C:A	donor_gain	1.0000
8:22227021:ACGTC:A	acceptor_gain	1.0000
8:22227022:CGTC:C	acceptor_gain	1.0000

AlphaMissense

2214 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:22221371:G:C	N325K	1.000
8:22221371:G:T	N325K	1.000
8:22221374:G:C	C324W	1.000
8:22221375:C:A	C324F	1.000
8:22221375:C:T	C324Y	1.000
8:22221376:A:G	C324R	1.000
8:22221383:G:C	C321W	1.000
8:22221384:C:A	C321F	1.000
8:22221384:C:G	C321S	1.000
8:22221384:C:T	C321Y	1.000
8:22221385:A:G	C321R	1.000
8:22221385:A:T	C321S	1.000
8:22221665:G:C	C227W	1.000
8:22221666:C:T	C227Y	1.000
8:22221667:A:G	C227R	1.000
8:22221836:G:C	S170R	1.000
8:22221836:G:T	S170R	1.000
8:22221838:T:G	S170R	1.000
8:22226862:A:G	F110S	1.000
8:22226879:C:A	W104C	1.000
8:22226879:C:G	W104C	1.000
8:22226881:A:G	W104R	1.000
8:22226881:A:T	W104R	1.000
8:22226932:C:G	A87P	1.000
8:22226941:A:C	Y84D	1.000
8:22226941:A:G	Y84H	1.000
8:22226958:A:T	L78Q	1.000
8:22226960:G:C	F77L	1.000
8:22226960:G:T	F77L	1.000
8:22226961:A:C	F77C	1.000

dbSNP variants (sampled 300 via entrez): RS1000245474 (8:22220401 A>G), RS1000560317 (8:22230613 C>G,T), RS1000586732 (8:22230343 T>G), RS1001018355 (8:22233908 C>G), RS1001131738 (8:22228930 T>C,G), RS1001376530 (8:22223865 G>A), RS1001784459 (8:22232880 T>C), RS1001846102 (8:22229703 C>T), RS1001881627 (8:22226582 C>A,T), RS1002440646 (8:22230842 C>T), RS1002492257 (8:22220722 C>T), RS1002850480 (8:22227759 G>A), RS1002881630 (8:22227600 C>T), RS1003190571 (8:22225975 T>C), RS1003276981 (8:22221712 G>A,C)

Disease associations

OMIM: gene MIM:608511 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST001905_1	Hypertriglyceridemia	7.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004530	triglyceride measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

27 total (human), top 27 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases expression, increases methylation	2
Tretinoin	decreases expression	2
sotorasib	affects cotreatment, decreases expression	1
ethyl-p-hydroxybenzoate	decreases expression	1
mono-(2-ethylhexyl)phthalate	decreases expression	1
sulforaphane	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
cupric chloride	decreases expression	1
tamibarotene	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
trametinib	affects cotreatment, decreases expression	1
NVP-BKM120	decreases expression, affects cotreatment	1
Catechin	decreases expression, affects cotreatment	1
Lead	affects expression	1
Nickel	decreases expression	1
Niclosamide	increases expression	1
Phenylmercuric Acetate	affects cotreatment, decreases expression	1
Silicon Dioxide	decreases expression	1
Smoke	decreases expression	1
Testosterone	decreases expression	1
Tobacco Smoke Pollution	affects expression	1
1-Methyl-4-phenylpyridinium	increases expression	1
Aflatoxin B1	increases methylation	1
Okadaic Acid	increases expression	1
Copper Sulfate	increases expression	1

Clinical trials (associated diseases)

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