PHYHIPL

Summary

PHYHIPL (phytanoyl-CoA 2-hydroxylase interacting protein like, HGNC:29378) is a protein-coding gene on chromosome 10q21.1, encoding Phytanoyl-CoA hydroxylase-interacting protein-like (Q96FC7). May play a role in the development of the central system.

Located in cytoplasm.

Source: NCBI Gene 84457 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 37 total
• MANE Select transcript: NM_032439

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29378
Approved symbol	PHYHIPL
Name	phytanoyl-CoA 2-hydroxylase interacting protein like
Location	10q21.1
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1796, Em:AC025038.1
Ensembl gene	ENSG00000165443
Ensembl biotype	protein_coding
Entrez	84457

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 2 protein_coding, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000373878, ENST00000373880, ENST00000472199, ENST00000486074

RefSeq mRNA: 2 — MANE Select: NM_032439 NM_001143774, NM_032439

CCDS: CCDS44405, CCDS7254

Canonical transcript exons

ENST00000373880 — 5 exons

Exon	Start	End
ENSE00001461828	59176643	59176959
ENSE00003498328	59238588	59238705
ENSE00003510113	59236483	59236657
ENSE00003588986	59234304	59234500
ENSE00003848912	59245057	59247770

Expression profiles

Bgee: expression breadth ubiquitous, 199 present calls, max score 98.20.

FANTOM5 (CAGE): breadth broad, TPM avg 17.2084 / max 496.1981, expressed in 407 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
105019	15.5551	390
105018	0.8568	204
105020	0.4350	155
105021	0.2149	83
105022	0.1467	48

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
prefrontal cortex	UBERON:0000451	98.20	gold quality
postcentral gyrus	UBERON:0002581	98.02	gold quality
Brodmann (1909) area 9	UBERON:0013540	97.74	gold quality
hypothalamus	UBERON:0001898	97.42	gold quality
substantia nigra	UBERON:0002038	97.40	gold quality
parietal lobe	UBERON:0001872	97.35	gold quality
frontal cortex	UBERON:0001870	97.30	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	97.22	gold quality
medial globus pallidus	UBERON:0002477	97.19	gold quality
superior vestibular nucleus	UBERON:0007227	97.14	gold quality
midbrain	UBERON:0001891	97.11	gold quality
substantia nigra pars compacta	UBERON:0001965	97.07	gold quality
medulla oblongata	UBERON:0001896	97.01	gold quality
globus pallidus	UBERON:0001875	96.98	gold quality
corpus callosum	UBERON:0002336	96.95	gold quality
neocortex	UBERON:0001950	96.90	gold quality
superior frontal gyrus	UBERON:0002661	96.85	gold quality
ventricular zone	UBERON:0003053	96.82	gold quality
amygdala	UBERON:0001876	96.76	gold quality
ganglionic eminence	UBERON:0004023	96.73	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	96.71	gold quality
right frontal lobe	UBERON:0002810	96.69	gold quality
pons	UBERON:0000988	96.66	gold quality
spinal cord	UBERON:0002240	96.59	gold quality
substantia nigra pars reticulata	UBERON:0001966	96.56	gold quality
cerebral cortex	UBERON:0000956	96.53	gold quality
anterior cingulate cortex	UBERON:0009835	96.44	gold quality
Brodmann (1909) area 46	UBERON:0006483	96.33	gold quality
subthalamic nucleus	UBERON:0001906	96.19	gold quality
temporal lobe	UBERON:0001871	96.18	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-6701	yes	16.33
E-ANND-3	yes	4.80

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): IRX1

miRNA regulators (miRDB)

170 targeting PHYHIPL, 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-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-4795-3P	100.00	74.62	4024
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-6740-5P	100.00	65.64	932
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-548A-5P	99.94	71.27	3482

Literature-anchored findings (GeneRIF, showing 2)

• Protein-protein interactions (PPI) net indicated that PHYHIPL may play a vital role in cell metabolism, and authors hypothesize that the downregulation mechanism may be the result of mutations of the ss-catenin gene and the endogenous siRNA, as shown in previous studies. (PMID:30962415)
• The Ser19Stop single nucleotide polymorphism (SNP) of human PHYHIPL affects the cerebellum in mice. (PMID:33712038)

Cross-species orthologs

10 orthologs

Organism	Symbol	Gene ID
danio_rerio	phyhipla	ENSDARG00000003998
danio_rerio	phyhiplb	ENSDARG00000070498
mus_musculus	Phyhipl	ENSMUSG00000037747
rattus_norvegicus	Phyhipl	ENSRNOG00000000274
caenorhabditis_elegans		WBGENE00010803
caenorhabditis_elegans		WBGENE00011697
caenorhabditis_elegans	Y92H12BR.7	WBGENE00022372
caenorhabditis_elegans		WBGENE00045337
caenorhabditis_elegans		WBGENE00045338
caenorhabditis_elegans		WBGENE00045339

Paralogs (1): PHYHIP (ENSG00000168490)

Protein

Protein identifiers

Phytanoyl-CoA hydroxylase-interacting protein-like — Q96FC7 (reviewed: Q96FC7)

All UniProt accessions (1): Q96FC7

UniProt curated annotations — full annotation on UniProt →

Function. May play a role in the development of the central system.

Similarity. Belongs to the PHYHIP family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q96FC7-1	1	yes
Q96FC7-2	2
Q96FC7-3	3

RefSeq proteins (2): NP_001137246, NP_115815* (*=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: PF00041, PF19281

UniProt features (11 total): modified residue 3, splice variant 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-Q96FC7-F1	82.85	0.65

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): 12, 15, 25

Glycosylation sites (2): 23, 37

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 136 (showing top): BENPORATH_ES_WITH_H3K27ME3, GCM_PTPRD, GCM_ZNF198, chr10q21, TACAATC_MIR508, CHIANG_LIVER_CANCER_SUBCLASS_INTERFERON_DN, CHIANG_LIVER_CANCER_SUBCLASS_CTNNB1_UP, GCM_MAP1B, NRSF_01, GCM_PTK2, YGCGYRCGC_UNKNOWN, CAGTGTT_MIR141_MIR200A, MIKKELSEN_MCV6_HCP_WITH_H3K27ME3, ATGAAGG_MIR205, KOYAMA_SEMA3B_TARGETS_DN

GO Biological Process (0):

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

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

960 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PHYHIPL	TMA16	Q96EY4	586
PHYHIPL	PHACTR3	Q96KR7	466
PHYHIPL	TMEM143	Q96AN5	447
PHYHIPL	EEF1AKMT1	Q8WVE0	391
PHYHIPL	ZSWIM3	Q96MP5	389
PHYHIPL	C2orf49	Q9BVC5	383
PHYHIPL	ARRDC2	Q8TBH0	373
PHYHIPL	FAM131A	Q6UXB0	370
PHYHIPL	ZNF23	P17027	362
PHYHIPL	TMEM186	Q96B77	358
PHYHIPL	COMTD1	Q86VU5	357
PHYHIPL	RASGEF1C	Q8N431	354
PHYHIPL	C5orf24	Q7Z6I8	349
PHYHIPL	KBTBD12	Q3ZCT8	348
PHYHIPL	IQCE	Q6IPM2	347

IntAct

24 interactions, top by confidence:

A	B	Type	Score
PDE9A	PHYHIPL	psi-mi:“MI:0915”(physical association)	0.560
MEI4	PHYHIPL	psi-mi:“MI:0915”(physical association)	0.560
PHYHIP	TRIP6	psi-mi:“MI:0914”(association)	0.530
PHYHIPL	RPS4Y1	psi-mi:“MI:0915”(physical association)	0.400
PHYHIPL	SMCHD1	psi-mi:“MI:0915”(physical association)	0.400
PHYHIPL		psi-mi:“MI:0915”(physical association)	0.370
PHYHIPL	HSPB1	psi-mi:“MI:0915”(physical association)	0.370
PDE9A	PHYHIPL	psi-mi:“MI:0915”(physical association)	0.370
PHYHIPL	GAPDH	psi-mi:“MI:0914”(association)	0.350
PHYHIPL	ATP5F1B	psi-mi:“MI:0914”(association)	0.350
PHYHIPL	NDUFAB1	psi-mi:“MI:0914”(association)	0.350
PHYHIPL	ACOT7	psi-mi:“MI:0914”(association)	0.350
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350
GPM6A	KIF2A	psi-mi:“MI:0914”(association)	0.350
DNAAF2	DNM1L	psi-mi:“MI:0914”(association)	0.350
TMCO6	UBB	psi-mi:“MI:0914”(association)	0.350
PACSIN1	PHYHIPL	psi-mi:“MI:0915”(physical association)	0.000
PHYHIPL	PDE9A	psi-mi:“MI:0915”(physical association)	0.000
PHYHIPL	MEI4	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (26): PHYHIPL (Two-hybrid), PHYHIPL (Affinity Capture-MS), PHYHIPL (Two-hybrid), PHYHIPL (Two-hybrid), PHYHIPL (Affinity Capture-MS), OPA3 (Affinity Capture-MS), LOC102724023 (Affinity Capture-MS), DHRS4 (Affinity Capture-MS), PMPCB (Affinity Capture-MS), STARD7 (Affinity Capture-MS), ECH1 (Affinity Capture-MS), C1QBP (Affinity Capture-MS), ACOT7 (Affinity Capture-MS), PHYHIPL (Two-hybrid), PHYHIPL (Affinity Capture-MS)

ESM2 similar proteins: A0A1L8H579, A0A1P8ARG1, A0A3B7TNW2, A1XIQ0, A2XTW9, A3CEM4, B2ZCQ2, B2ZCQ3, C6EN00, F4I1X0, F5HAI6, I1R9B4, I6LJ77, O36416, O76616, O96624, P09003, P09004, P0DUE1, P11468, P15718, P21299, P29476, P40587, Q02330, Q06003, Q20A00, Q23376, Q2QYR5, Q32L96, Q39072, Q3E8K6, Q58FY4, Q5R4W4, Q66WT5, Q6AYN4, Q7X9V2, Q89759, Q8BGT8, Q8H6Z6

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

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
IRX1	“down-regulates quantity by repression”	PHYHIPL	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	35
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2031 predictions. Top by Δscore:

Variant	Effect	Δscore
10:59220224:A:G	acceptor_gain	1.0000
10:59234299:T:A	acceptor_gain	1.0000
10:59234299:TGCA:T	acceptor_loss	1.0000
10:59234300:GCA:G	acceptor_loss	1.0000
10:59234301:CA:C	acceptor_loss	1.0000
10:59234302:A:AC	acceptor_loss	1.0000
10:59234302:A:AG	acceptor_gain	1.0000
10:59234302:AG:A	acceptor_gain	1.0000
10:59234302:AGG:A	acceptor_gain	1.0000
10:59234303:G:GT	acceptor_gain	1.0000
10:59234303:GG:G	acceptor_gain	1.0000
10:59234303:GGG:G	acceptor_gain	1.0000
10:59234303:GGGA:G	acceptor_gain	1.0000
10:59234303:GGGAA:G	acceptor_gain	1.0000
10:59234498:AAGG:A	donor_loss	1.0000
10:59234499:AGGTA:A	donor_loss	1.0000
10:59234500:GGTAA:G	donor_loss	1.0000
10:59234501:G:T	donor_loss	1.0000
10:59234502:T:A	donor_loss	1.0000
10:59236482:GGAT:G	acceptor_gain	1.0000
10:59236656:AG:A	donor_loss	1.0000
10:59236657:GG:G	donor_loss	1.0000
10:59236658:G:C	donor_loss	1.0000
10:59236659:T:A	donor_loss	1.0000
10:59238586:A:AG	acceptor_gain	1.0000
10:59238587:G:GG	acceptor_gain	1.0000
10:59238587:GACT:G	acceptor_gain	1.0000
10:59238642:G:GT	donor_gain	1.0000
10:59238702:TTCGG:T	donor_loss	1.0000
10:59238703:TCGG:T	donor_loss	1.0000

AlphaMissense

2512 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:59234355:C:A	P53Q	1.000
10:59234387:G:C	D64H	1.000
10:59234388:A:T	D64V	1.000
10:59234390:T:C	S65P	1.000
10:59234393:T:C	F66L	1.000
10:59234394:T:C	F66S	1.000
10:59234395:C:A	F66L	1.000
10:59234395:C:G	F66L	1.000
10:59234405:T:A	W70R	1.000
10:59234405:T:C	W70R	1.000
10:59234444:T:G	Y83D	1.000
10:59234447:T:C	F84L	1.000
10:59234448:T:C	F84S	1.000
10:59234448:T:G	F84C	1.000
10:59234449:T:A	F84L	1.000
10:59234449:T:G	F84L	1.000
10:59234457:T:A	L87H	1.000
10:59234457:T:C	L87P	1.000
10:59234489:T:C	F98L	1.000
10:59234490:T:C	F98S	1.000
10:59234491:T:A	F98L	1.000
10:59234491:T:G	F98L	1.000
10:59236487:T:A	V103D	1.000
10:59236489:C:A	P104T	1.000
10:59236489:C:T	P104S	1.000
10:59236490:C:A	P104H	1.000
10:59236490:C:G	P104R	1.000
10:59236495:A:G	K106E	1.000
10:59236496:A:T	K106I	1.000
10:59236497:A:C	K106N	1.000

dbSNP variants (sampled 300 via entrez): RS1000011126 (10:59199593 A>T), RS1000025609 (10:59182178 G>A,C), RS1000038081 (10:59218411 T>C), RS1000046302 (10:59216003 T>C), RS1000123463 (10:59175473 T>C), RS1000131481 (10:59180239 G>A,T), RS1000150792 (10:59218831 T>C), RS1000248449 (10:59188103 A>G), RS1000267304 (10:59219117 C>T), RS1000305234 (10:59209632 G>A), RS1000421185 (10:59205999 G>A), RS1000447040 (10:59203168 G>A,C,T), RS1000463544 (10:59203455 G>T), RS1000484565 (10:59173907 C>A,T), RS1000579272 (10:59213707 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

2 associations (top):

Study	Trait	p-value
GCST003518_34	Daytime sleep phenotypes	4.000000e-06
GCST003542_26	Night sleep phenotypes	3.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007828	daytime rest measurement
EFO:0007827	nighttime rest measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
FR900359	decreases phosphorylation	1
bisphenol F	affects cotreatment, increases methylation	1
2,4,6-tribromophenol	decreases expression	1
bisphenol A	affects expression	1
sodium arsenate	increases expression, increases abundance	1
decabromobiphenyl ether	decreases expression	1
terbufos	increases methylation	1
tetrabromobisphenol A	decreases expression	1
4-aminophenylarsenoxide	affects binding, decreases reaction	1
beta-methylcholine	affects expression	1
K 7174	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
Sunitinib	decreases expression	1
Arsenic Trioxide	affects binding, decreases reaction	1
Fulvestrant	affects cotreatment, increases methylation	1
Arsenic	increases abundance, increases expression	1
Benzo(a)pyrene	decreases methylation, increases methylation	1
Cytarabine	increases expression	1
Fonofos	increases methylation	1
Parathion	increases methylation	1
Quercetin	decreases expression	1
Triclosan	decreases expression	1
Tunicamycin	decreases expression	1
Urethane	decreases expression	1
Valproic Acid	increases expression	1
Cyclosporine	decreases expression	1
Okadaic Acid	decreases expression	1
beta-Naphthoflavone	increases expression	1

Clinical trials (associated diseases)

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