FAM9C

Summary

FAM9C (family with sequence similarity 9 member C, HGNC:18405) is a protein-coding gene on chromosome Xp22.2, encoding Protein FAM9C (Q8IZT9).

This gene is a member of a gene family which arose through duplication on the X chromosome. The encoded protein may be localized to the nucleus as the protein contains several nuclear localization signals, and has similarity to a synaptonemal complex protein.

Source: NCBI Gene 171484 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 25 total
• MANE Select transcript: NM_174901

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18405
Approved symbol	FAM9C
Name	family with sequence similarity 9 member C
Location	Xp22.2
Locus type	gene with protein product
Status	Approved
Aliases	TEX39C
Ensembl gene	ENSG00000187268
Ensembl biotype	protein_coding
OMIM	300479
Entrez	171484

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 4 protein_coding, 1 retained_intron

ENST00000333995, ENST00000380625, ENST00000438997, ENST00000468287, ENST00000542843

RefSeq mRNA: 1 — MANE Select: NM_174901 NM_174901

CCDS: CCDS35203

Canonical transcript exons

ENST00000380625 — 8 exons

Exon	Start	End
ENSE00001334858	13040758	13040872
ENSE00001334859	13042918	13042949
ENSE00003546984	13038416	13038503
ENSE00003552142	13043128	13043248
ENSE00003582243	13043729	13043857
ENSE00003582432	13039808	13039916
ENSE00003848605	13035617	13036018
ENSE00003849457	13044540	13044620

Expression profiles

Bgee: expression breadth broad, 95 present calls, max score 82.47.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.9431 / max 599.2058, expressed in 37 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
198442	0.9109	37
198443	0.0323	11

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	82.47	gold quality
apex of heart	UBERON:0002098	75.57	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	75.54	gold quality
secondary oocyte	CL:0000655	66.65	silver quality
oocyte	CL:0000023	64.09	silver quality
right testis	UBERON:0004534	63.66	gold quality
spleen	UBERON:0002106	62.61	gold quality
testis	UBERON:0000473	61.57	gold quality
left testis	UBERON:0004533	61.04	gold quality
lower lobe of lung	UBERON:0008949	58.96	silver quality
cortical plate	UBERON:0005343	57.83	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	56.73	gold quality
cardiac muscle of right atrium	UBERON:0003379	54.34	gold quality
left ventricle myocardium	UBERON:0006566	54.23	gold quality
kidney epithelium	UBERON:0004819	53.93	gold quality
upper arm skin	UBERON:0004263	53.52	gold quality
epithelial cell of pancreas	CL:0000083	53.16	gold quality
left ovary	UBERON:0002119	50.84	gold quality
ovary	UBERON:0000992	50.73	gold quality
deltoid	UBERON:0001476	50.63	gold quality
calcaneal tendon	UBERON:0003701	50.55	gold quality
myocardium	UBERON:0002349	50.25	gold quality
stromal cell of endometrium	CL:0002255	49.51	gold quality
ganglionic eminence	UBERON:0004023	49.25	gold quality
heart left ventricle	UBERON:0002084	48.96	gold quality
cardiac ventricle	UBERON:0002082	48.72	gold quality
quadriceps femoris	UBERON:0001377	48.70	gold quality
biceps brachii	UBERON:0001507	48.54	gold quality
tibialis anterior	UBERON:0001385	48.41	silver quality
nasal cavity epithelium	UBERON:0005384	48.38	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-6678	yes	217.91
E-ANND-3	yes	4.08

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

33 targeting FAM9C, 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-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-4282	99.99	75.36	6408
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-377-5P	99.70	65.28	712
HSA-MIR-6086	99.70	65.38	699
HSA-MIR-1303	99.65	69.77	1662
HSA-MIR-4666B	99.64	68.69	1282
HSA-MIR-892A	99.54	68.16	1141
HSA-MIR-6740-3P	99.48	68.49	1392
HSA-MIR-4735-5P	99.43	68.49	1780
HSA-MIR-297	99.40	69.58	1418
HSA-MIR-4427	99.34	70.33	1854
HSA-MIR-421	98.90	67.04	1883
HSA-MIR-1288-5P	98.85	67.01	734
HSA-MIR-5197-3P	98.71	67.05	1905
HSA-MIR-302F	98.44	69.02	1776
HSA-MIR-4704-3P	98.28	69.33	1300
HSA-MIR-943	97.81	64.42	694
HSA-MIR-4799-3P	97.78	65.97	893
HSA-MIR-4720-5P	97.46	65.67	893
HSA-MIR-5588-5P	97.46	65.70	913
HSA-MIR-219B-3P	97.31	66.96	672

Literature-anchored findings (GeneRIF, showing 2)

• Expressed exclusively in testis; protein is located in the nucleus. (PMID:12213195)
• FAM9C overexpression increased the phosphorylation levels of Akt and anti-apoptotic ability in hepatocellular carcinoma. (PMID:23836295)

Cross-species orthologs

21 orthologs

Organism	Symbol	Gene ID
danio_rerio	sycp3	ENSDARG00000013438
mus_musculus	Xlr4c	ENSMUSG00000031362
mus_musculus	Xlr3a	ENSMUSG00000057836
mus_musculus	Xlr3c	ENSMUSG00000058147
mus_musculus	Xlr5a	ENSMUSG00000058328
mus_musculus	Xlr5c	ENSMUSG00000067764
mus_musculus	Xlr4b	ENSMUSG00000067768
mus_musculus	Xlr5b	ENSMUSG00000072479
mus_musculus	Xlr3b	ENSMUSG00000073125
mus_musculus	Gm14692	ENSMUSG00000079577
mus_musculus	Gm1140	ENSMUSG00000079578
mus_musculus	Xlr4a	ENSMUSG00000079845
rattus_norvegicus	Xlr5c	ENSRNOG00000050177
rattus_norvegicus	Xlr4a	ENSRNOG00000055822
rattus_norvegicus	Fam9cl1	ENSRNOG00000062315
rattus_norvegicus	LOC100911047	ENSRNOG00000064693
rattus_norvegicus	LOC100911047	ENSRNOG00000068104
rattus_norvegicus	Fam9c	ENSRNOG00000069253
rattus_norvegicus		ENSRNOG00000075733
rattus_norvegicus		ENSRNOG00000087898
rattus_norvegicus		ENSRNOG00000088563

Paralogs (3): SYCP3 (ENSG00000139351), FAM9B (ENSG00000177138), FAM9A (ENSG00000183304)

Protein

Protein identifiers

Protein FAM9C — Q8IZT9 (reviewed: Q8IZT9)

All UniProt accessions (3): Q8IZT9, G3V1I3, H7C346

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Nucleus.

Tissue specificity. Expressed exclusively in testis.

Similarity. Belongs to the XLR/SYCP3 family.

RefSeq proteins (1): NP_777561* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006888	XLR/SYCP3/FAM9_dom	Domain
IPR051443	XLR/SYCP3	Family

Pfam: PF04803

UniProt features (6 total): compositionally biased region 3, region of interest 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IZT9-F1	78.22	0.46

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 47 (showing top): GOBP_MALE_GAMETE_GENERATION, GERY_CEBP_TARGETS, SCHAEFFER_PROSTATE_DEVELOPMENT_12HR_UP, COATES_MACROPHAGE_M1_VS_M2_UP, GOBP_CELLULAR_PROCESS_INVOLVED_IN_REPRODUCTION_IN_MULTICELLULAR_ORGANISM, AFFAR_YY1_TARGETS_UP, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, JACKSON_DNMT1_TARGETS_UP, CHEN_ETV5_TARGETS_TESTIS, HOWLIN_CITED1_TARGETS_1_DN, GOBP_MEIOTIC_CELL_CYCLE, BOYLAN_MULTIPLE_MYELOMA_PCA3_UP, GOCC_NUCLEAR_CHROMOSOME, GOCC_CONDENSED_NUCLEAR_CHROMOSOME, chrXp22

GO Biological Process (2): spermatid development (GO:0007286), meiotic cell cycle (GO:0051321)

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

GO Cellular Component (3): synaptonemal complex (GO:0000795), nucleus (GO:0005634), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
germ cell development	1
spermatid differentiation	1
cell cycle	1
sexual reproduction	1
reproductive process	1
meiotic nuclear division	1
binding	1
synaptonemal structure	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

700 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FAM9C	CCDC191	Q8NCU4	623
FAM9C	Q15513	Q15513	621
FAM9C	TEX30	Q5JUR7	533
FAM9C	OR2T11	Q8NH01	507
FAM9C	TEX29	Q8N6K0	484
FAM9C	KRTAP17-1	Q9BYP8	478
FAM9C	TEX13C	A0A0J9YWL9	447
FAM9C	RPA4	Q13156	373
FAM9C	SAMD12	Q8N8I0	360
FAM9C	TEX36	Q5VZQ5	353
FAM9C	PPP2R2A	P50409	350
FAM9C	TEX12	Q9BXU0	349
FAM9C	DPY19L2	Q6NUT2	348
FAM9C	S100Z	Q8WXG8	348
FAM9C	TEX13D	A0A0J9YY54	348
FAM9C	ARL15	Q9NXU5	348

IntAct

44 interactions, top by confidence:

A	B	Type	Score
SNAP29	FAM9C	psi-mi:“MI:0915”(physical association)	0.740
FAM9C	SNAP29	psi-mi:“MI:0914”(association)	0.740
FAM9C	TPM3	psi-mi:“MI:0915”(physical association)	0.720
TPM3	FAM9C	psi-mi:“MI:0915”(physical association)	0.720
SKA1	FAM9C	psi-mi:“MI:0915”(physical association)	0.670
NDC80	FAM9C	psi-mi:“MI:0915”(physical association)	0.670
FAM9C	SKA1	psi-mi:“MI:0915”(physical association)	0.670
FAM9C	NDC80	psi-mi:“MI:0914”(association)	0.670
FAM9C	TPM3	psi-mi:“MI:0915”(physical association)	0.560
TPM3	FAM9C	psi-mi:“MI:0915”(physical association)	0.560
SNAPC5	FAM9C	psi-mi:“MI:0915”(physical association)	0.560
TRIML2	FAM9C	psi-mi:“MI:0915”(physical association)	0.560
TEX12	FAM9C	psi-mi:“MI:0915”(physical association)	0.560
BORCS6	FAM9C	psi-mi:“MI:0915”(physical association)	0.560
FAM9C	TEX12	psi-mi:“MI:0915”(physical association)	0.560
TPM1	FAM9C	psi-mi:“MI:0915”(physical association)	0.560
ABI2	FAM9C	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (68): FAM9C (Two-hybrid), FAM9C (Two-hybrid), FAM9C (Two-hybrid), FAM9C (Two-hybrid), FAM9C (Two-hybrid), FAM9C (Two-hybrid), FAM9C (Two-hybrid), FAM9C (Two-hybrid), FAM9C (Two-hybrid), FAM9C (Two-hybrid), C17orf59 (Two-hybrid), MINA (Affinity Capture-MS), CCNC (Affinity Capture-MS), CEP44 (Affinity Capture-MS), EXOC1 (Affinity Capture-MS)

ESM2 similar proteins: A7TJT3, B3EWV0, C0HLQ3, O31159, O66093, O66096, O91083, P0C1J9, P0C1K3, P0C1K4, P0C8M3, P0CA74, P21016, P24360, P33868, P52531, P80745, P82331, P83602, P84712, P86298, P86299, P86300, P86301, P86302, P86305, P86307, P86309, P86310, P86688, Q02838, Q1A264, Q27976, Q44160, Q46490, Q54C30, Q54KW6, Q54PY5, Q54V15, Q54X31

Diamond homologs: Q8IZT9, Q8IZU0, Q8IZU1, Q4R764, Q8IZU3

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	17
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1736 predictions. Top by Δscore:

Variant	Effect	Δscore
X:13038499:ATTTT:A	acceptor_gain	1.0000
X:13038500:TTTT:T	acceptor_gain	1.0000
X:13038501:TTT:T	acceptor_gain	1.0000
X:13038501:TTTC:T	acceptor_loss	1.0000
X:13038502:TT:T	acceptor_gain	1.0000
X:13038504:C:CC	acceptor_gain	1.0000
X:13038505:T:C	acceptor_loss	1.0000
X:13038511:C:CT	acceptor_gain	1.0000
X:13039793:AAG:A	donor_gain	1.0000
X:13039794:AG:A	donor_gain	1.0000
X:13039804:CAAC:C	donor_loss	1.0000
X:13039806:A:AC	donor_gain	1.0000
X:13039807:C:CC	donor_gain	1.0000
X:13039807:CA:C	donor_gain	1.0000
X:13039807:CAA:C	donor_gain	1.0000
X:13039818:T:TA	donor_gain	1.0000
X:13039819:C:A	donor_gain	1.0000
X:13039836:T:A	donor_gain	1.0000
X:13039913:CTGC:C	acceptor_gain	1.0000
X:13039914:TGC:T	acceptor_gain	1.0000
X:13039917:C:CC	acceptor_gain	1.0000
X:13039917:CT:C	acceptor_loss	1.0000
X:13039918:T:A	acceptor_loss	1.0000
X:13040701:CAA:C	acceptor_gain	1.0000
X:13040702:A:T	acceptor_gain	1.0000
X:13040752:TCATA:T	donor_loss	1.0000
X:13040753:CATA:C	donor_loss	1.0000
X:13040754:ATACC:A	donor_loss	1.0000
X:13040755:TAC:T	donor_loss	1.0000
X:13040756:A:AT	donor_loss	1.0000

AlphaMissense

1115 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:13039862:G:C	F128L	0.930
X:13039862:G:T	F128L	0.930
X:13039864:A:G	F128L	0.930
X:13039884:A:G	L121S	0.923
X:13039910:T:A	K112N	0.886
X:13039910:T:G	K112N	0.886
X:13038495:A:C	F149L	0.882
X:13038495:A:T	F149L	0.882
X:13038497:A:G	F149L	0.882
X:13039908:C:G	R113P	0.875
X:13040844:C:A	K81N	0.837
X:13040844:C:G	K81N	0.837
X:13040764:A:G	L108P	0.819
X:13039916:C:A	R110S	0.809
X:13039916:C:G	R110S	0.809
X:13039914:T:G	Q111P	0.807
X:13040760:T:A	K109N	0.795
X:13040760:T:G	K109N	0.795
X:13038474:C:A	W156C	0.778
X:13038474:C:G	W156C	0.778
X:13039911:T:A	K112I	0.771
X:13039911:T:G	K112T	0.763
X:13040845:T:A	K81M	0.762
X:13039913:C:A	Q111H	0.756
X:13039913:C:G	Q111H	0.756
X:13038483:T:A	Q153H	0.751
X:13038483:T:G	Q153H	0.751
X:13043151:A:C	F53L	0.751
X:13043151:A:T	F53L	0.751
X:13043153:A:G	F53L	0.751

dbSNP variants (sampled 300 via entrez): RS1001940813 (X:13035202 T>C), RS1002288798 (X:13044986 C>T), RS1002360695 (X:13044560 C>T), RS1003205845 (X:13038430 C>T), RS1003310734 (X:13037219 G>A,T), RS1003374 (X:13045231 T>C,G), RS1003646551 (X:13037868 T>C), RS1004419916 (X:13045774 T>A), RS1004854806 (X:13045089 G>T), RS1006272996 (X:13035241 G>A), RS1007031741 (X:13045648 A>G), RS1007494831 (X:13036312 A>G), RS1007835149 (X:13036917 TC>T), RS1008506121 (X:13043474 G>A), RS1009098594 (X:13039696 G>A)

Disease associations

OMIM: gene MIM:300479 | 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
GCST007798_115	Asthma	6.000000e-12
GCST007800_91	Asthma (childhood onset)	8.000000e-14

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

6 total (human), top 6 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
4-aminophenylarsenoxide	decreases reaction, affects binding	1
CGP 52608	affects binding, increases reaction	1
Arsenic Trioxide	affects binding, decreases reaction	1
Benzo(a)pyrene	decreases expression	1
Silicon Dioxide	decreases expression	1
Okadaic Acid	increases expression	1

Clinical trials (associated diseases)

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