PHTF1

Summary

PHTF1 (putative homeodomain transcription factor 1, HGNC:8939) is a protein-coding gene on chromosome 1p13.2, encoding Protein PHTF1 (Q9UMS5).

Predicted to be located in cis-Golgi network membrane and endoplasmic reticulum membrane.

Source: NCBI Gene 10745 — RefSeq curated summary.

At a glance

• GWAS associations: 11
• Clinical variants (ClinVar): 147 total
• MANE Select transcript: NM_001323043

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8939
Approved symbol	PHTF1
Name	putative homeodomain transcription factor 1
Location	1p13.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000116793
Ensembl biotype	protein_coding
OMIM	604950
Entrez	10745

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 13 protein_coding, 5 protein_coding_CDS_not_defined

ENST00000357783, ENST00000369598, ENST00000369600, ENST00000369604, ENST00000393357, ENST00000412670, ENST00000446739, ENST00000472612, ENST00000474926, ENST00000481652, ENST00000486855, ENST00000493212, ENST00000873091, ENST00000873092, ENST00000873093, ENST00000873094, ENST00000930186, ENST00000969008

RefSeq mRNA: 14 — MANE Select: NM_001323043 NM_001323041, NM_001323042, NM_001323043, NM_001323044, NM_001323045, NM_001323046, NM_001323047, NM_001323048, NM_001323049, NM_001323050, NM_001323051, NM_001323052, NM_001323053, NM_006608

CCDS: CCDS81359, CCDS861

Canonical transcript exons

ENST00000369604 — 19 exons

Exon	Start	End
ENSE00001450425	113758659	113758733
ENSE00001603086	113724759	113724893
ENSE00001651027	113713279	113713438
ENSE00001805853	113738730	113738799
ENSE00003466622	113711746	113711835
ENSE00003467911	113705890	113706162
ENSE00003507078	113706594	113706722
ENSE00003545554	113757699	113757755
ENSE00003573030	113738110	113738268
ENSE00003599966	113710254	113710475
ENSE00003600401	113699704	113699799
ENSE00003670016	113698262	113698387
ENSE00003676591	113704081	113704167
ENSE00003680476	113726418	113726574
ENSE00003681397	113711940	113712113
ENSE00003683211	113704666	113704797
ENSE00003686829	113700794	113700949
ENSE00003846785	113759023	113759486
ENSE00003848732	113696831	113697725

Expression profiles

Bgee: expression breadth ubiquitous, 224 present calls, max score 93.59.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 24.3323 / max 201.6748, expressed in 1816 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
13906	21.8275	1812
13905	1.2859	763
13904	0.5249	220
13901	0.4550	149
13903	0.2390	106

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	93.59	gold quality
cerebellar hemisphere	UBERON:0002245	93.50	gold quality
cerebellar cortex	UBERON:0002129	93.35	gold quality
secondary oocyte	CL:0000655	91.98	gold quality
cerebellum	UBERON:0002037	91.14	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	90.77	gold quality
sperm	CL:0000019	90.06	gold quality
ventricular zone	UBERON:0003053	88.57	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	88.55	gold quality
left testis	UBERON:0004533	88.33	gold quality
right testis	UBERON:0004534	88.32	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.81	gold quality
male germ cell	CL:0000015	87.72	gold quality
testis	UBERON:0000473	87.61	gold quality
adenohypophysis	UBERON:0002196	87.38	gold quality
stromal cell of endometrium	CL:0002255	87.07	gold quality
pituitary gland	UBERON:0000007	86.47	gold quality
right frontal lobe	UBERON:0002810	86.30	gold quality
adrenal tissue	UBERON:0018303	85.74	gold quality
islet of Langerhans	UBERON:0000006	85.69	gold quality
right lung	UBERON:0002167	85.54	gold quality
ganglionic eminence	UBERON:0004023	85.40	gold quality
bronchial epithelial cell	CL:0002328	85.19	gold quality
calcaneal tendon	UBERON:0003701	84.94	gold quality
oocyte	CL:0000023	84.86	gold quality
right uterine tube	UBERON:0001302	84.66	gold quality
right adrenal gland	UBERON:0001233	84.64	gold quality
right adrenal gland cortex	UBERON:0035827	84.50	gold quality
left adrenal gland	UBERON:0001234	84.10	gold quality
monocyte	CL:0000576	84.06	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-HCAD-6	yes	43.69
E-ANND-3	yes	6.27
E-CURD-10	no	125.27

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

25 targeting PHTF1, 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-3925-3P	100.00	69.95	1237
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-448	99.79	72.37	2103
HSA-MIR-6817-3P	99.79	68.35	2126
HSA-MIR-3680-3P	99.75	72.51	3095
HSA-MIR-545-5P	99.66	70.18	2308
HSA-MIR-766-3P	99.47	65.24	1811
HSA-MIR-5584-3P	99.23	68.79	1351
HSA-MIR-548L	99.06	70.90	2560
HSA-MIR-1304-3P	98.29	66.44	1207
HSA-MIR-1914-5P	97.83	66.21	807
HSA-MIR-4712-5P	97.24	67.79	775
HSA-MIR-770-5P	97.24	68.10	758
HSA-MIR-3976	96.67	67.79	1187
HSA-MIR-500B-3P	96.49	65.40	1087
HSA-MIR-10525-3P	96.32	68.04	699
HSA-MIR-1298-5P	95.96	64.81	573
HSA-MIR-7706	95.96	63.68	172

Literature-anchored findings (GeneRIF, showing 1)

• Results supports the rs6679677 (PHTF1-PTPN22) SNP as a susceptibility factor for type 1 diabetes. (PMID:20089178)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	phtf1	ENSDARG00000057708
mus_musculus	Phtf1	ENSMUSG00000058388
rattus_norvegicus	Phtf1	ENSRNOG00000019785
drosophila_melanogaster	phtf	FBGN0028579

Paralogs (1): PHTF2 (ENSG00000006576)

Protein

Protein identifiers

Protein PHTF1 — Q9UMS5 (reviewed: Q9UMS5)

All UniProt accessions (5): Q9UMS5, F6T5D1, H0Y825, Q5TCQ3, Q5TCQ5

UniProt curated annotations — full annotation on UniProt →

Subunit / interactions. Interacts with FEM1B.

Subcellular location. Endoplasmic reticulum membrane. Golgi apparatus. cis-Golgi network membrane.

Tissue specificity. Widely expressed with highest levels in testis.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9UMS5-1	1	yes
Q9UMS5-2	2

RefSeq proteins (14): NP_001309970, NP_001309971, NP_001309972, NP_001309973, NP_001309974, NP_001309975, NP_001309976, NP_001309977, NP_001309978, NP_001309979, NP_001309980, NP_001309981, NP_001309982, NP_006599 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR021980	PHTF1/2_N	Domain
IPR039775	PHTF1/2	Family

Pfam: PF12129

UniProt features (33 total): transmembrane region 8, glycosylation site 6, modified residue 5, sequence conflict 5, region of interest 3, compositionally biased region 2, splice variant 2, chain 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UMS5-F1	62.01	0.15

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 (5): 272, 276, 277, 334, 336

Glycosylation sites (6): 179, 180, 363, 431, 674, 733

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 0 (showing top):

GO Biological Process (0):

GO Molecular Function (0):

GO Cellular Component (4): endoplasmic reticulum membrane (GO:0005789), Golgi apparatus (GO:0005794), endoplasmic reticulum (GO:0005783), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	2
endomembrane system	2
intracellular membrane-bounded organelle	2
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1156 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PHTF1	HNF1A	P20823	791
PHTF1	MAGI3	Q5TCQ9	729
PHTF1	RSBN1	Q5VWQ0	698
PHTF1	BCL2L15	Q5TBC7	650
PHTF1	PTPN22	Q9Y2R2	610
PHTF1	AP4B1	Q9Y6B7	507
PHTF1	DCLRE1B	Q9H816	506
PHTF1	COMMD2	Q86X83	490
PHTF1	SWT1	Q5T5J6	488
PHTF1	FEM1B	Q9UK73	482
PHTF1	TRIML2	Q8N7C3	457
PHTF1	ELP5	Q8TE02	457
PHTF1	PISD	Q9UG56	435
PHTF1	DNAJB6	O75190	418
PHTF1	QRFPR	Q96P65	417

IntAct

8 interactions, top by confidence:

A	B	Type	Score
GPR156	PLD2	psi-mi:“MI:0914”(association)	0.640
PHTF1	H2AC4	psi-mi:“MI:0915”(physical association)	0.400
PHTF1	CAPN5	psi-mi:“MI:0915”(physical association)	0.400
HOXB9	PHTF1	psi-mi:“MI:0915”(physical association)	0.370
	HAX1	psi-mi:“MI:0914”(association)	0.350
PHTF2	STXBP1	psi-mi:“MI:0914”(association)	0.350
PHTF2	OSBPL3	psi-mi:“MI:0914”(association)	0.350

BioGRID (23): CAPN5 (Affinity Capture-MS), PHTF1 (Affinity Capture-MS), PHTF1 (Affinity Capture-MS), PHTF1 (Affinity Capture-RNA), PHTF1 (Proximity Label-MS), PHTF1 (Affinity Capture-MS), CAPN5 (Affinity Capture-MS), PHTF1 (Affinity Capture-MS), PHTF1 (Cross-Linking-MS (XL-MS)), PHTF1 (Cross-Linking-MS (XL-MS)), PHTF1 (Cross-Linking-MS (XL-MS)), PHTF1 (Cross-Linking-MS (XL-MS)), PHTF1 (Cross-Linking-MS (XL-MS)), PHTF1 (Cross-Linking-MS (XL-MS)), PHTF1 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A0JPH4, A7MBC7, D3ZWZ9, F1M8G0, F1QFU0, F4JTN2, O14524, P0C152, P49653, Q08DA4, Q0IJ20, Q148L1, Q28EW0, Q3TPR7, Q4V8X0, Q5HYA8, Q5M7W4, Q5R9R1, Q5RDB4, Q5RH73, Q5U308, Q5VW38, Q5ZKN3, Q6AXF6, Q6P6V6, Q6Q3F5, Q6ZQE4, Q7L1W4, Q7ZYA0, Q86V85, Q8BGR2, Q8BKU8, Q8BPS4, Q8BR76, Q8BUV8, Q8BXN9, Q8CB19, Q8N3S3, Q8NBN3, Q8R4P4

Diamond homologs: F1M8G0, Q08DA4, Q5ZKN3, Q8CB19, Q8N3S3, Q9QZ09, Q9UMS5, Q9V9A8

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	107
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3128 predictions. Top by Δscore:

Variant	Effect	Δscore
1:113697723:CAG:C	acceptor_gain	1.0000
1:113698260:A:AC	donor_gain	1.0000
1:113698261:C:CC	donor_gain	1.0000
1:113698261:CT:C	donor_gain	1.0000
1:113698384:GCTCC:G	acceptor_loss	1.0000
1:113698385:CTCCT:C	acceptor_loss	1.0000
1:113698389:T:A	acceptor_loss	1.0000
1:113706032:G:C	donor_gain	1.0000
1:113710238:T:C	donor_gain	1.0000
1:113710253:CCTG:C	donor_gain	1.0000
1:113710267:T:TA	donor_gain	1.0000
1:113710323:A:AC	donor_gain	1.0000
1:113710324:C:CC	donor_gain	1.0000
1:113710474:CC:C	acceptor_gain	1.0000
1:113710474:CCCTT:C	acceptor_gain	1.0000
1:113710475:CC:C	acceptor_gain	1.0000
1:113710476:C:CC	acceptor_gain	1.0000
1:113710476:C:T	acceptor_gain	1.0000
1:113710477:T:TC	acceptor_gain	1.0000
1:113710478:T:C	acceptor_gain	1.0000
1:113710478:T:TC	acceptor_gain	1.0000
1:113711740:CTTTA:C	donor_loss	1.0000
1:113711741:TTTAC:T	donor_loss	1.0000
1:113711742:TTA:T	donor_loss	1.0000
1:113711743:TACC:T	donor_loss	1.0000
1:113711745:C:A	donor_loss	1.0000
1:113711745:CCTGG:C	donor_gain	1.0000
1:113711831:TTTAC:T	acceptor_gain	1.0000
1:113711835:CCTG:C	acceptor_loss	1.0000
1:113711836:C:CA	acceptor_loss	1.0000

AlphaMissense

4992 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:113699723:A:G	L708P	1.000
1:113699729:A:G	L706S	1.000
1:113699750:A:G	L699P	1.000
1:113699786:A:G	L687P	1.000
1:113704670:A:G	L600P	1.000
1:113704682:A:G	L596P	1.000
1:113704692:A:G	W593R	1.000
1:113704692:A:T	W593R	1.000
1:113704718:A:G	L584P	1.000
1:113704718:A:T	L584H	1.000
1:113704724:A:G	F582S	1.000
1:113704728:G:C	H581D	1.000
1:113704730:G:C	P580R	1.000
1:113704730:G:T	P580H	1.000
1:113704748:G:T	A574D	1.000
1:113704754:C:A	R572M	1.000
1:113704761:A:G	S570P	1.000
1:113706662:A:G	W444R	1.000
1:113706662:A:T	W444R	1.000
1:113726491:C:G	G139R	1.000
1:113726491:C:T	G139R	1.000
1:113738212:C:A	G77W	1.000
1:113738212:C:G	G77R	1.000
1:113738212:C:T	G77R	1.000
1:113757731:A:G	W24R	1.000
1:113757731:A:T	W24R	1.000
1:113697722:A:G	W758R	0.999
1:113697722:A:T	W758R	0.999
1:113698271:A:C	F753L	0.999
1:113698271:A:T	F753L	0.999

dbSNP variants (sampled 300 via entrez): RS1000135258 (1:113757897 A>G), RS1000197231 (1:113723236 G>A), RS1000229929 (1:113716716 T>A,C,G), RS1000236832 (1:113702065 C>G,T), RS1000242644 (1:113750720 G>C), RS1000299730 (1:113750914 C>T), RS1000329943 (1:113703704 A>G), RS1000439530 (1:113710241 T>C,G), RS1000522903 (1:113715002 C>G), RS1000560139 (1:113713550 G>A), RS1000560996 (1:113734349 G>T), RS1000578603 (1:113752505 A>G), RS1000584282 (1:113760961 G>A), RS1000632435 (1:113752792 T>A), RS1000632870 (1:113758451 T>C)

Disease associations

OMIM: gene MIM:604950 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST000038_9	Type 1 diabetes	8.000000e-24
GCST001474_13	Hypothyroidism	3.000000e-13
GCST001762_676	Obesity-related traits	2.000000e-06
GCST001958_8	Bulimia nervosa	6.000000e-06
GCST002876_9	Type 1 diabetes and autoimmune thyroid diseases	7.000000e-20
GCST004132_97	Crohn’s disease	4.000000e-06
GCST004866_5	Alopecia areata	7.000000e-07
GCST008870_69	Keratinocyte cancer (MTAG)	7.000000e-11
GCST008871_75	Basal cell carcinoma	2.000000e-14
GCST90002380_79	Basophil percentage of white cells	2.000000e-16
GCST90002398_490	Neutrophil count	3.000000e-25

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0005134	amino acid measurement
EFO:0010176	keratinocyte carcinoma
EFO:0007992	basophil percentage of leukocytes
EFO:0004833	neutrophil count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs6679677	PHTF1, RSBN1		0.00	0

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	affects expression, increases abundance, decreases expression	2
Benzo(a)pyrene	decreases methylation, increases expression	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
sotorasib	affects cotreatment, increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases methylation	1
geraniol	increases expression	1
trichostatin A	decreases expression	1
cobaltous chloride	increases expression	1
butyraldehyde	decreases expression	1
manganese chloride	decreases expression	1
cupric oxide	increases expression	1
beta-methylcholine	affects expression	1
pentabromodiphenyl ether	decreases expression	1
cylindrospermopsin	decreases expression	1
ICG 001	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
trametinib	affects cotreatment, increases expression	1
NVP-BKM120	affects cotreatment, increases expression	1
Bortezomib	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Temozolomide	decreases expression	1
Sunitinib	decreases expression	1
Vehicle Emissions	increases abundance, increases expression	1
Cisplatin	increases expression	1
Coumestrol	increases expression, affects cotreatment	1
Folic Acid	decreases expression	1
Manganese	decreases expression	1
Methyl Methanesulfonate	increases expression	1
Ozone	affects expression, increases abundance	1

Clinical trials (associated diseases)

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