PMF1

Summary

PMF1 (polyamine modulated factor 1, HGNC:9112) is a protein-coding gene on chromosome 1q22, encoding Polyamine-modulated factor 1 (Q6P1K2). Part of the MIS12 complex which is required for normal chromosome alignment and segregation and kinetochore formation during mitosis. It is a common-essential gene (DepMap: required in 99.3% of cancer cell lines).

Enables leucine zipper domain binding activity and transcription coactivator activity. Involved in chromosome segregation. Located in Golgi apparatus; kinetochore; and nucleoplasm. Part of MIS12/MIND type complex. Implicated in bladder carcinoma and urinary bladder cancer.

Source: NCBI Gene 11243 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 29 total — 1 pathogenic
• Cancer dependency (DepMap): dependent in 99.3% of screened cell lines (common-essential)
• MANE Select transcript: NM_007221

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9112
Approved symbol	PMF1
Name	polyamine modulated factor 1
Location	1q22
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000160783
Ensembl biotype	protein_coding
OMIM	609176
Entrez	11243

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 13 protein_coding, 2 nonsense_mediated_decay, 1 retained_intron

ENST00000368273, ENST00000368277, ENST00000368279, ENST00000466489, ENST00000497069, ENST00000606952, ENST00000868456, ENST00000868457, ENST00000868458, ENST00000868459, ENST00000868460, ENST00000920596, ENST00000920597, ENST00000920598, ENST00000960527, ENST00000960528

RefSeq mRNA: 10 — MANE Select: NM_007221 NM_001199653, NM_001199654, NM_001393909, NM_001393910, NM_001393911, NM_001393912, NM_001393913, NM_001393914, NM_001393915, NM_007221

CCDS: CCDS30886, CCDS55648, CCDS55649

Canonical transcript exons

ENST00000368277 — 5 exons

Exon	Start	End
ENSE00001446751	156239548	156240042
ENSE00003467403	156213007	156213176
ENSE00003545659	156236288	156236483
ENSE00003622958	156232320	156232425
ENSE00003627097	156233628	156233728

Expression profiles

Bgee: expression breadth ubiquitous, 278 present calls, max score 96.53.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 66.3410 / max 748.2458, expressed in 1817 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
5702	66.3410	1817

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
hindlimb stylopod muscle	UBERON:0004252	96.53	gold quality
apex of heart	UBERON:0002098	96.15	gold quality
right lobe of thyroid gland	UBERON:0001119	95.28	gold quality
left lobe of thyroid gland	UBERON:0001120	95.27	gold quality
gastrocnemius	UBERON:0001388	95.19	gold quality
metanephros cortex	UBERON:0010533	95.12	gold quality
muscle of leg	UBERON:0001383	95.06	gold quality
right atrium auricular region	UBERON:0006631	94.73	gold quality
ectocervix	UBERON:0012249	94.65	gold quality
skin of leg	UBERON:0001511	94.64	gold quality
thyroid gland	UBERON:0002046	94.63	gold quality
heart left ventricle	UBERON:0002084	94.58	gold quality
granulocyte	CL:0000094	94.54	gold quality
skin of abdomen	UBERON:0001416	94.50	gold quality
cardiac ventricle	UBERON:0002082	94.40	gold quality
monocyte	CL:0000576	94.37	gold quality
right lobe of liver	UBERON:0001114	94.33	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	94.32	gold quality
endocervix	UBERON:0000458	94.20	gold quality
body of uterus	UBERON:0009853	94.13	gold quality
mononuclear cell	CL:0000842	94.11	gold quality
leukocyte	CL:0000738	94.03	gold quality
right uterine tube	UBERON:0001302	93.96	gold quality
body of stomach	UBERON:0001161	93.88	gold quality
left ovary	UBERON:0002119	93.86	gold quality
right lung	UBERON:0002167	93.82	gold quality
cardiac atrium	UBERON:0002081	93.78	gold quality
heart	UBERON:0000948	93.66	gold quality
minor salivary gland	UBERON:0001830	93.64	gold quality
right ovary	UBERON:0002118	93.64	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NFE2L2, TBP, VDR

miRNA regulators (miRDB)

20 targeting PMF1, 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-1252-5P	100.00	69.80	2774
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-6073	99.60	70.36	793
HSA-MIR-762	99.58	66.61	1994
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-185-5P	99.35	68.60	2497
HSA-MIR-4644	99.35	69.12	2514
HSA-MIR-6837-5P	99.25	65.47	1632
HSA-MIR-4685-5P	99.25	65.99	1563
HSA-MIR-5693	99.24	66.67	1106
HSA-MIR-3925-5P	99.21	67.90	1466
HSA-MIR-5001-5P	99.05	66.76	1972
HSA-MIR-1178-3P	98.57	67.09	890
HSA-MIR-6847-5P	97.93	66.74	1808
HSA-MIR-6747-5P	96.17	64.99	743
HSA-MIR-6805-5P	95.79	64.86	670
HSA-MIR-12115	94.19	66.37	738

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.3% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 4)

• Polyamine-modulated factor 1 binds to CSN7. (PMID:12020345)
• The association of PMF1 methylation with tumor progression and its diagnostic ability using urinary specimens support including PMF1 assessment for the clinical management of bladder cancer patients. (PMID:19088041)
• Bladder carcinoma with unmethylated PMF1 was more likely to recur after BCG treatment. (PMID:22682992)
• These results suggest that rs1052053 in PMF1 is not associated with leukoaraiosis (LA) risk in the Chinese population. (PMID:27583843)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	si:dkey-6i22.5	ENSDARG00000077822
mus_musculus	Pmf1	ENSMUSG00000028066
rattus_norvegicus	Pmf1	ENSRNOG00000019620

Protein

Protein identifiers

Polyamine-modulated factor 1 — Q6P1K2 (reviewed: Q6P1K2)

All UniProt accessions (3): Q6P1K2, V9GYH6, V9GYI0

UniProt curated annotations — full annotation on UniProt →

Function. Part of the MIS12 complex which is required for normal chromosome alignment and segregation and kinetochore formation during mitosis. May act as a cotranscription partner of NFE2L2 involved in regulation of polyamine-induced transcription of SSAT.

Subunit / interactions. Component of the MIS12 complex composed of MIS12, DSN1, NSL1 and PMF1. Interacts with COPS7A. Interacts via its coiled-coil domain with the leucine-zipper domain of NFE2L2. The interaction with NFE2L2 is required for the transcriptional regulation of SSAT.

Subcellular location. Nucleus. Chromosome. Centromere. Kinetochore.

Tissue specificity. Highest levels of expression in heart and skeletal muscle, with significant levels expressed in kidney and liver.

Induction. By polyamine analogs in analog-sensitive H157 cells.

Isoforms (6)

UniProt ID	Names	Canonical?
Q6P1K2-1	1	yes
Q6P1K2-2	2
Q6P1K2-3	3
Q6P1K2-4	4
Q6P1K2-5	5
Q6P1K2-6	6

RefSeq proteins (10): NP_001186582, NP_001186583, NP_001380838, NP_001380839, NP_001380840, NP_001380841, NP_001380842, NP_001380843, NP_001380844, NP_009152* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007128	PMF1/Nnf1	Family

Pfam: PF03980

UniProt features (19 total): helix 7, splice variant 6, sequence variant 2, chain 1, region of interest 1, sequence conflict 1, coiled-coil region 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
8PPR	ELECTRON MICROSCOPY	3
5LSJ	X-RAY DIFFRACTION	3.25
5LSK	X-RAY DIFFRACTION	3.5
8Q5H	ELECTRON MICROSCOPY	4.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6P1K2-F1	88.35	0.80

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-141444	Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal
R-HSA-2467813	Separation of Sister Chromatids
R-HSA-2500257	Resolution of Sister Chromatid Cohesion
R-HSA-5663220	RHO GTPases Activate Formins
R-HSA-68877	Mitotic Prometaphase
R-HSA-9648025	EML4 and NUDC in mitotic spindle formation

MSigDB gene sets: 183 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_DN, GOBP_ATTACHMENT_OF_SPINDLE_MICROTUBULES_TO_KINETOCHORE, GOBP_CHROMOSOME_LOCALIZATION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, TAL1ALPHAE47_01, YY1_Q6, MUELLER_PLURINET, MORF_FANCG, chr1q22, AFP1_Q6, AACTTT_UNKNOWN, MORF_PML, SPIELMAN_LYMPHOBLAST_EUROPEAN_VS_ASIAN_UP, FISCHER_DREAM_TARGETS

GO Biological Process (5): transcription by RNA polymerase II (GO:0006366), chromosome segregation (GO:0007059), attachment of spindle microtubules to kinetochore (GO:0008608), cell division (GO:0051301), positive regulation of DNA-templated transcription (GO:0045893)

GO Molecular Function (3): transcription coactivator activity (GO:0003713), leucine zipper domain binding (GO:0043522), protein binding (GO:0005515)

GO Cellular Component (11): MIS12/MIND type complex (GO:0000444), kinetochore (GO:0000776), spindle pole (GO:0000922), outer kinetochore (GO:0000940), nucleus (GO:0005634), nucleoplasm (GO:0005654), transcription regulator complex (GO:0005667), Golgi apparatus (GO:0005794), cytosol (GO:0005829), chromosome, centromeric region (GO:0000775), chromosome (GO:0005694)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Mitotic Prometaphase	2
Amplification of signal from the kinetochores	1
Mitotic Anaphase	1
RHO GTPase Effectors	1
M Phase	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
DNA-templated transcription	2
cell cycle process	2
intracellular membraneless organelle	2
protein-containing complex	2
intracellular membrane-bounded organelle	2
cytoplasm	2
microtubule binding	1
metaphase chromosome alignment	1
cellular process	1
regulation of DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
transcription coregulator activity	1
positive regulation of DNA-templated transcription	1
LRR domain binding	1
binding	1
outer kinetochore	1
condensed chromosome, centromeric region	1
supramolecular complex	1
spindle	1
kinetochore	1
nuclear lumen	1
endomembrane system	1
chromosomal region	1

Protein interactions and networks

STRING

728 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PMF1	DSN1	Q9H410	998
PMF1	NSL1	Q96IY1	949
PMF1	SAT1	P21673	909
PMF1	NFE2L2	Q16236	906
PMF1	ZWINT	O95229	889
PMF1	KNL1	Q8NG31	814
PMF1	CBX5	P45973	693
PMF1	SLC25A44	Q96H78	677
PMF1	CENPT	Q96BT3	659
PMF1	GCLM	P48507	644
PMF1	PMFBP1	Q8TBY8	626
PMF1	SPC24	Q8NBT2	590
PMF1	KEAP1	Q14145	571
PMF1	CENPC	Q03188	550
PMF1	CBX3	Q13185	536

IntAct

143 interactions, top by confidence:

A	B	Type	Score
MIS12	PMF1	psi-mi:“MI:0915”(physical association)	0.950
PMF1	MIS12	psi-mi:“MI:0915”(physical association)	0.950
PMF1	MIS12	psi-mi:“MI:2364”(proximity)	0.950
MIS12	PMF1	psi-mi:“MI:2364”(proximity)	0.950
ZWINT	NDC80	psi-mi:“MI:0914”(association)	0.940
SPC25	NDC80	psi-mi:“MI:0914”(association)	0.940
SPC24	NDC80	psi-mi:“MI:0914”(association)	0.920
DSN1	ZWINT	psi-mi:“MI:0914”(association)	0.900
MIS12	ZWINT	psi-mi:“MI:0914”(association)	0.900
DTNB	DMD	psi-mi:“MI:0914”(association)	0.890
MIS12	NDC80	psi-mi:“MI:0914”(association)	0.850
DSN1	NDC80	psi-mi:“MI:0914”(association)	0.790
PPP1CC	CCDC85C	psi-mi:“MI:0914”(association)	0.740

BioGRID (210): MIS12 (Two-hybrid), USHBP1 (Two-hybrid), PMF1 (Affinity Capture-MS), PMF1 (Affinity Capture-MS), PMF1 (Affinity Capture-MS), PMF1 (Affinity Capture-MS), SGTB (Affinity Capture-MS), SEC63 (Affinity Capture-MS), PGRMC2 (Affinity Capture-MS), ZRANB1 (Affinity Capture-MS), WDR45B (Affinity Capture-MS), GNPAT (Affinity Capture-MS), PPP1CC (Affinity Capture-MS), ZMPSTE24 (Affinity Capture-MS), CMTM6 (Affinity Capture-MS)

ESM2 similar proteins: A1A4V9, A4IFQ0, A6NFY4, A6QNT4, G3HKI1, O60443, P50747, Q13426, Q13769, Q14159, Q1JQA1, Q1RMS8, Q2HJ93, Q2HJB9, Q2KHT6, Q3T1H6, Q3ZK22, Q5E9K8, Q5FVM3, Q5M7Q1, Q5RFG8, Q5RFL7, Q5XI52, Q5ZJK1, Q641X7, Q68FX7, Q6NZQ0, Q6P1K2, Q7YS54, Q7Z6J8, Q8BX13, Q8C5K5, Q8CHQ0, Q8K2I9, Q8NFZ0, Q8QZS3, Q8TCJ0, Q8VE91, Q91WC1, Q91Z62

Diamond homologs: Q2T9N4, Q6P1K2, Q9CPV5

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
PMF1	“form complex”	“MIS12 complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 87 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Amplification of signal from the kinetochores	9	29.5×	8e-10
Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal	13	25.2×	9e-13
Mitotic Spindle Checkpoint	9	23.8×	5e-09
EML4 and NUDC in mitotic spindle formation	13	20.1×	9e-12
Resolution of Sister Chromatid Cohesion	13	18.7×	2e-11
RHO GTPases Activate Formins	13	16.8×	5e-11
Cell Cycle Checkpoints	11	16.2×	3e-09
Mitotic Prometaphase	13	15.0×	2e-10

GO biological processes:

GO term	Partners	Fold	FDR
attachment of spindle microtubules to kinetochore	7	86.2×	3e-10
attachment of mitotic spindle microtubules to kinetochore	5	69.3×	1e-06
mitotic spindle assembly checkpoint signaling	8	59.1×	3e-10
mitotic sister chromatid segregation	5	31.7×	5e-05
mitotic spindle organization	5	17.9×	8e-04
chromosome segregation	7	16.0×	4e-05
cell division	15	9.1×	2e-08

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	24
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
665025	NC_000001.11:g.(?156114919)(156243162_?)del	Pathogenic

SpliceAI

1294 predictions. Top by Δscore:

Variant	Effect	Δscore
1:156213174:C:T	donor_gain	1.0000
1:156213174:CAGGT:C	donor_loss	1.0000
1:156213175:AGGT:A	donor_loss	1.0000
1:156213175:AGGTA:A	donor_loss	1.0000
1:156213176:GG:G	donor_loss	1.0000
1:156213177:G:A	donor_loss	1.0000
1:156213177:GTAAA:G	donor_loss	1.0000
1:156213178:T:G	donor_loss	1.0000
1:156233623:TTCA:T	acceptor_loss	1.0000
1:156233624:TCAG:T	acceptor_loss	1.0000
1:156233625:CAG:C	acceptor_loss	1.0000
1:156233626:A:AC	acceptor_loss	1.0000
1:156233626:A:AG	acceptor_gain	1.0000
1:156233626:AGGAG:A	acceptor_gain	1.0000
1:156233627:G:GG	acceptor_gain	1.0000
1:156233627:G:GT	acceptor_loss	1.0000
1:156233627:GGA:G	acceptor_gain	1.0000
1:156233627:GGAGG:G	acceptor_gain	1.0000
1:156233705:C:T	donor_gain	1.0000
1:156233724:GCCTG:G	donor_gain	1.0000
1:156233726:CTGG:C	donor_loss	1.0000
1:156233727:TGGT:T	donor_loss	1.0000
1:156233729:G:GG	donor_gain	1.0000
1:156233729:GTG:G	donor_loss	1.0000
1:156236481:CAG:C	donor_loss	1.0000
1:156236484:GTC:G	donor_loss	1.0000
1:156232314:C:A	acceptor_gain	0.9900
1:156232318:A:AG	acceptor_gain	0.9900
1:156232319:G:GG	acceptor_gain	0.9900
1:156233624:TCAGG:T	acceptor_gain	0.9900

AlphaMissense

1343 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:156232330:T:C	F58L	0.969
1:156232332:C:A	F58L	0.969
1:156232332:C:G	F58L	0.969
1:156233648:A:C	K96N	0.966
1:156233648:A:T	K96N	0.966
1:156233727:T:A	W123R	0.965
1:156233727:T:C	W123R	0.965
1:156232331:T:C	F58S	0.964
1:156236289:C:A	R124S	0.960
1:156213148:T:C	F45L	0.951
1:156213150:T:A	F45L	0.951
1:156213150:T:G	F45L	0.951
1:156232409:T:C	L84S	0.947
1:156236290:G:C	R124P	0.944
1:156236288:G:C	W123C	0.942
1:156236288:G:T	W123C	0.942
1:156236428:G:C	R170P	0.930
1:156236295:A:C	S126R	0.914
1:156236297:C:A	S126R	0.914
1:156236297:C:G	S126R	0.914
1:156213161:T:C	L49P	0.911
1:156213152:T:C	L46P	0.909
1:156236315:T:A	D132E	0.908
1:156236315:T:G	D132E	0.908
1:156236314:A:C	D132A	0.905
1:156233674:T:C	L105S	0.904
1:156232331:T:G	F58C	0.901
1:156232421:T:A	I88N	0.901
1:156233662:T:C	L101P	0.900
1:156236313:G:C	D132H	0.896

dbSNP variants (sampled 300 via entrez): RS1000095661 (1:156220216 G>A,T), RS1000125308 (1:156238150 A>G), RS1000184287 (1:156212364 T>G), RS1000233679 (1:156225358 G>A,C), RS1000295157 (1:156219022 A>G), RS1000325635 (1:156219278 T>G), RS1000549679 (1:156237890 T>C), RS1000611464 (1:156212788 A>C), RS1000772971 (1:156231756 A>G,T), RS1000840787 (1:156223832 C>G,T), RS1000900002 (1:156237712 G>A), RS1000935993 (1:156230290 G>A,C), RS1000966991 (1:156230483 T>C), RS1001032606 (1:156219254 C>A,T), RS1001067983 (1:156212356 C>T)

Disease associations

OMIM: gene MIM:609176 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): Charcot-Marie-Tooth disease type 2 (MONDO:0018993)

Orphanet (1): Autosomal dominant Charcot-Marie-Tooth disease type 2 (Orphanet:64746)

HPO phenotypes

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

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST002389_1	Intracerebral hemorrhage	2.000000e-10
GCST003013_36	White matter hyperintensity burden	2.000000e-08
GCST005352_28	Paclitaxel disposition in epithelial ovarian cancer	6.000000e-06
GCST007344_48	Estimated glomerular filtration rate	1.000000e-08
GCST008601_4	Longevity (age >99th survival percentile)	1.000000e-06
GCST008876_5	Non-lobar intracerebral hemorrhage (MTAG)	3.000000e-08
GCST009066_32	Mosaic loss of chromosome Y (Y chromosome dosage)	2.000000e-36
GCST009067_23	Mosaic loss of chromosome Y (Y chromosome dosage)	3.000000e-88
GCST009375_5	Mosaic loss of chromosome Y (Y chromosome dosage)	2.000000e-19

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0005665	white matter hyperintensity measurement
EFO:0010178	non-lobar intracerebral hemorrhage
EFO:0007783	mosaic loss of chromosome Y measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

19 total (human), top 19 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, increases methylation	4
TAK-243	increases sumoylation	1
triphenyl phosphate	affects expression	1
propionaldehyde	decreases expression	1
methoxyacetic acid	decreases expression	1
beta-lapachone	decreases expression, increases expression	1
cobaltous chloride	decreases expression	1
beta-methylcholine	affects expression	1
Vorinostat	decreases expression	1
Arsenic	affects methylation	1
Atrazine	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Cadmium	decreases expression	1
Diuron	decreases expression	1
Doxorubicin	affects expression	1
Fluorouracil	affects reaction, decreases expression	1
Smoke	decreases expression	1
Urethane	decreases expression	1
Copper Sulfate	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05902351	Not specified	RECRUITING	Natural History Study for Charcot Marie Tooth Disease