AP1S2 (adaptor related protein complex 1 subunit sigma 2)

Gene

• Entrez ID: 8905
• Gene name: Adaptor related protein complex 1 subunit sigma 2
• Gene symbol: AP1S2
• Synonyms (NCBI Gene): DC22, MRX59, MRXS21, MRXS5, MRXSF, PGS, SIGMA1B
• Chromosome: X
• Chromosome location: Xp22.2
• Summary: Adaptor protein complex 1 is found at the cytoplasmic face of coated vesicles located at the Golgi complex, where it mediates both the recruitment of clathrin to the membrane and the recognition of sorting signals within the cytosolic tails of transmembra

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs104894735	G>A	Pathogenic	Coding sequence variant, non coding transcript variant, stop gained
rs104894739	G>A	Pathogenic	Coding sequence variant, non coding transcript variant, stop gained
rs137852213	C>A	Pathogenic	Coding sequence variant, non coding transcript variant, stop gained
rs587776738	TGTA>-	Pathogenic	Splice acceptor variant, intron variant
rs587776739	C>T	Pathogenic	Intron variant
rs587777542	C>A	Pathogenic	Splice donor variant
rs886041964	G>-	Pathogenic	Non coding transcript variant, frameshift variant, coding sequence variant
rs1060499672	G>T	Pathogenic	Intron variant
rs1555904148	T>C	Pathogenic	Splice acceptor variant
rs1555904182	A>-	Pathogenic	Non coding transcript variant, frameshift variant, coding sequence variant
rs1555904878	G>A	Pathogenic	Non coding transcript variant, stop gained, coding sequence variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT005816	hsa-miR-204-5p	Luciferase reporter assay, Microarray, qRT-PCR	21282569
MIRT024614	hsa-miR-215-5p	Microarray	19074876
MIRT026570	hsa-miR-192-5p	Microarray	19074876
MIRT054445	hsa-miR-211-5p	Luciferase reporter assay, Microarray, qRT-PCR, Western blot	24039954
MIRT054445	hsa-miR-211-5p	HITS-CLIP	23824327
MIRT005816	hsa-miR-204-5p	HITS-CLIP	23824327
MIRT624728	hsa-miR-5580-3p	HITS-CLIP	23824327
MIRT624727	hsa-miR-3938	HITS-CLIP	23824327
MIRT624726	hsa-miR-6832-3p	HITS-CLIP	23824327
MIRT624725	hsa-miR-4504	HITS-CLIP	23824327
MIRT624724	hsa-miR-542-3p	HITS-CLIP	23824327
MIRT624723	hsa-miR-623	HITS-CLIP	23824327
MIRT624722	hsa-miR-4755-5p	HITS-CLIP	23824327
MIRT624721	hsa-miR-5006-3p	HITS-CLIP	23824327
MIRT624720	hsa-miR-2681-5p	HITS-CLIP	23824327
MIRT054445	hsa-miR-211-5p	HITS-CLIP	23824327
MIRT005816	hsa-miR-204-5p	HITS-CLIP	23824327
MIRT624728	hsa-miR-5580-3p	HITS-CLIP	23824327
MIRT624727	hsa-miR-3938	HITS-CLIP	23824327
MIRT624726	hsa-miR-6832-3p	HITS-CLIP	23824327
MIRT624725	hsa-miR-4504	HITS-CLIP	23824327
MIRT624724	hsa-miR-542-3p	HITS-CLIP	23824327
MIRT624723	hsa-miR-623	HITS-CLIP	23824327
MIRT624722	hsa-miR-4755-5p	HITS-CLIP	23824327
MIRT624721	hsa-miR-5006-3p	HITS-CLIP	23824327
MIRT624720	hsa-miR-2681-5p	HITS-CLIP	23824327
MIRT787270	hsa-miR-101	CLIP-seq
MIRT787271	hsa-miR-144	CLIP-seq
MIRT787272	hsa-miR-200b	CLIP-seq
MIRT787273	hsa-miR-200c	CLIP-seq
MIRT787274	hsa-miR-3121-5p	CLIP-seq
MIRT787275	hsa-miR-3617	CLIP-seq
MIRT787276	hsa-miR-3647-3p	CLIP-seq
MIRT787277	hsa-miR-3671	CLIP-seq
MIRT787278	hsa-miR-3913-3p	CLIP-seq
MIRT787279	hsa-miR-429	CLIP-seq
MIRT787280	hsa-miR-4310	CLIP-seq
MIRT787281	hsa-miR-4432	CLIP-seq
MIRT787282	hsa-miR-4729	CLIP-seq
MIRT787283	hsa-miR-4766-3p	CLIP-seq
MIRT787284	hsa-miR-4802-3p	CLIP-seq
MIRT787285	hsa-miR-548p	CLIP-seq
MIRT787286	hsa-miR-556-5p	CLIP-seq
MIRT787287	hsa-miR-600	CLIP-seq
MIRT787288	hsa-miR-610	CLIP-seq
MIRT787289	hsa-miR-641	CLIP-seq
MIRT1932224	hsa-miR-3065-5p	CLIP-seq
MIRT787277	hsa-miR-3671	CLIP-seq
MIRT1932225	hsa-miR-513a-3p	CLIP-seq
MIRT787272	hsa-miR-200b	CLIP-seq
MIRT787273	hsa-miR-200c	CLIP-seq
MIRT2172585	hsa-miR-3609	CLIP-seq
MIRT787275	hsa-miR-3617	CLIP-seq
MIRT2172586	hsa-miR-369-3p	CLIP-seq
MIRT787278	hsa-miR-3913-3p	CLIP-seq
MIRT787279	hsa-miR-429	CLIP-seq
MIRT2172587	hsa-miR-4318	CLIP-seq
MIRT2172588	hsa-miR-455-5p	CLIP-seq
MIRT2172589	hsa-miR-4693-5p	CLIP-seq
MIRT787283	hsa-miR-4766-3p	CLIP-seq
MIRT2172590	hsa-miR-548ah	CLIP-seq
MIRT787285	hsa-miR-548p	CLIP-seq
MIRT787287	hsa-miR-600	CLIP-seq
MIRT787289	hsa-miR-641	CLIP-seq
MIRT2172591	hsa-miR-892a	CLIP-seq
MIRT2426369	hsa-miR-204	CLIP-seq
MIRT2426370	hsa-miR-211	CLIP-seq
MIRT2475588	hsa-miR-365	CLIP-seq
MIRT2475589	hsa-miR-376c	CLIP-seq
MIRT2475590	hsa-miR-3976	CLIP-seq
MIRT2475591	hsa-miR-4272	CLIP-seq
MIRT2475592	hsa-miR-4275	CLIP-seq
MIRT2475593	hsa-miR-4777-3p	CLIP-seq
MIRT2475594	hsa-miR-494	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000139	Component	Golgi membrane	TAS
GO:0005515	Function	Protein binding	IPI	25416956, 26496610, 28514442, 29892012, 32296183, 33961781
GO:0005737	Component	Cytoplasm	IEA
GO:0005765	Component	Lysosomal membrane	NAS	23247405
GO:0005765	Component	Lysosomal membrane	TAS
GO:0005769	Component	Early endosome	NAS	23247405
GO:0005794	Component	Golgi apparatus	IDA
GO:0005794	Component	Golgi apparatus	IEA
GO:0005829	Component	Cytosol	TAS
GO:0005905	Component	Clathrin-coated pit	IEA
GO:0006886	Process	Intracellular protein transport	IEA
GO:0015031	Process	Protein transport	IEA
GO:0016020	Component	Membrane	IEA
GO:0016192	Process	Vesicle-mediated transport	IBA
GO:0016192	Process	Vesicle-mediated transport	IEA
GO:0016192	Process	Vesicle-mediated transport	NAS	23247405
GO:0030117	Component	Membrane coat	IEA
GO:0030119	Component	AP-type membrane coat adaptor complex	TAS	9733768
GO:0030121	Component	AP-1 adaptor complex	IEA
GO:0030121	Component	AP-1 adaptor complex	NAS	15377783
GO:0030659	Component	Cytoplasmic vesicle membrane	IEA
GO:0030659	Component	Cytoplasmic vesicle membrane	TAS
GO:0031410	Component	Cytoplasmic vesicle	IEA
GO:0032588	Component	Trans-Golgi network membrane	NAS	15377783
GO:0032588	Component	Trans-Golgi network membrane	TAS
GO:0035615	Function	Clathrin adaptor activity	IEA
GO:0043231	Component	Intracellular membrane-bounded organelle	IBA
GO:0060155	Process	Platelet dense granule organization	NAS	23247405
GO:1903232	Process	Melanosome assembly	NAS	23247405

Other IDs

• MIM: 300629
• HGNC: 560
• e!Ensembl: ENSG00000182287

Protein

• UniProt ID: P56377
• Protein name: AP-1 complex subunit sigma-2 (Adaptor protein complex AP-1 subunit sigma-1B) (Adaptor-related protein complex 1 subunit sigma-1B) (Clathrin assembly protein complex 1 sigma-1B small chain) (Golgi adaptor HA1/AP1 adaptin sigma-1B subunit) (Sigma 1B subunit
• Protein function: Subunit of clathrin-associated adaptor protein complex 1 that plays a role in protein sorting in the late-Golgi/trans-Golgi network (TGN) and/or endosomes. The AP complexes mediate both the recruitment of clathrin to membranes and the recognitio
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF01217	Clat_adaptor_s	1 → 141	Clathrin adaptor complex small chain	Domain

• Tissue specificity: TISSUE SPECIFICITY: Widely expressed.
• Sequence:

  MQFMLLFSRQGKLRLQKWYVPLSDKEKKKITRELVQTVLARKPKMCSFLEWRDLKIVYKR
  YASLYFCCAIEDQDNELITLEIIHRYVELLDKYFGSVCELDIIFNFEKAYFILDEFLLGG
  EVQETSKKNVLKAIEQADLLQEEAETPRSVLEEIGLT

• Sequence length: 157

Pathways

KEGG:

Lysosome
Human immunodeficiency virus 1 infection

Reactome:

Nef mediated downregulation of MHC class I complex cell surface expression
MHC class II antigen presentation
Lysosome Vesicle Biogenesis
Golgi Associated Vesicle Biogenesis

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Fried syndrome	Pathogenic	rs1555904878	RCV001824840	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Pettigrew syndrome	Pathogenic; Likely pathogenic	rs587777542, rs2519915767, rs2519929822, rs2519914292, rs104894739, rs104894735, rs587776738, rs587776739, rs137852213, rs2519914351, rs1060499672, rs1555904182, rs1555904878, rs1934288587, rs1933972061, rs1934209113	RCV000128636 RCV003149130 RCV003153171 RCV004798977 RCV000011524 RCV000011525 RCV000011526 RCV000011527 RCV000011528 RCV004586090 RCV000449627 RCV000504312 RCV001824840 RCV001194623 RCV001248805 RCV001270029	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Thyroid cancer, nonmedullary, 1	Pathogenic	rs1934209113	RCV005910799	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Acute myeloid leukemia	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
AP1S2-related disorder	Uncertain significance; Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
AUTISM SPECTRUM DISORDER	—	GenCC	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
AUTISM SPECTRUM DISORDERS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Clear cell carcinoma of kidney	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Colon adenocarcinoma	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Gastric cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hepatocellular carcinoma	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
LIVER CIRRHOSIS, EXPERIMENTAL	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant lymphoma, large B-cell, diffuse	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Melanoma	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MENTAL RETARDATION, X-LINKED, SYNDROMIC 5	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PARTINGTON SYNDROME	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Sarcoma	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine carcinosarcoma	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine corpus endometrial carcinoma	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
X-LINKED INTELLECTUAL DISABILITY AND HYPOTONIA WITH FACIAL DYSMORPHISM AND AGGRESSIVE BEHAVIOR SYNDROME	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
X-LINKED INTELLECTUAL DISABILITY-DANDY-WALKER MALFORMATION-BASAL GANGLIA DISEASE-SEIZURES SYNDROME	—	Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
X-LINKED INTELLECTUAL DISABILITY-HYPOTONIA-FACIAL DYSMORPHISM-AGGRESSIVE BEHAVIOR SYNDROME	—	Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
X-LINKED SYNDROMIC COMPLEX NEURODEVELOPMENTAL DISORDER	—	ClinGen, GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Aicardi Goutieres syndrome	Aicardi goutieres syndrome	Pubtator	17617514	Associate	★☆☆☆☆ Found in Text Mining only
Autistic behavior	Autism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Autistic Disorder	Autism	BEFREE	18428203		★☆☆☆☆ Found in Text Mining only
Azoospermia Nonobstructive	Nonobstructive azoospermia	Pubtator	38403804	Associate	★☆☆☆☆ Found in Text Mining only
Basal Ganglia Diseases	Basal ganglia disease	Pubtator	23756445	Associate	★☆☆☆☆ Found in Text Mining only
Body Weight	Body weight	Pubtator	35178801	Stimulate	★☆☆☆☆ Found in Text Mining only
Breast Carcinoma	Breast Carcinoma	BEFREE	31019021		★☆☆☆☆ Found in Text Mining only
Breast Neoplasms	Breast neoplasm	Pubtator	31019021	Associate	★☆☆☆☆ Found in Text Mining only
Byzanthine arch palate	High palate	HPO_DG			★☆☆☆☆ Found in Text Mining only
Cerebral cortical atrophy	Cerebral cortical atrophy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Choreoathetosis	Choreoathetosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Class III malocclusion	Malocclusion	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congenital anomaly of face	Facial dysmorphism	BEFREE	23756445		★☆☆☆☆ Found in Text Mining only
Congenital Hydrocephalus	Congenital Hydrocephalus	BEFREE	28556411		★☆☆☆☆ Found in Text Mining only
Coronary Arteriosclerosis	Coronary Arteriosclerosis	BEFREE	31211779		★☆☆☆☆ Found in Text Mining only
Coronary Artery Disease	Coronary artery disease	BEFREE	31211779		★☆☆☆☆ Found in Text Mining only
Coronary heart disease	Coronary Heart Disease	BEFREE	31211779		★☆☆☆☆ Found in Text Mining only
Cryptorchidism	Cryptorchidism	HPO_DG			★☆☆☆☆ Found in Text Mining only
DANDY-WALKER MALFORMATION WITH MENTAL RETARDATION, BASAL GANGLIA DISEASE, AND SEIZURES	Pettigrew syndrome	CTD_human_DG	17186471, 17617514, 23756445		★☆☆☆☆ Found in Text Mining only
DANDY-WALKER MALFORMATION WITH MENTAL RETARDATION, BASAL GANGLIA DISEASE, AND SEIZURES	Pettigrew syndrome	GENOMICS_ENGLAND_DG	1842820, 18428203, 23756445		★☆☆☆☆ Found in Text Mining only
DANDY-WALKER MALFORMATION WITH MENTAL RETARDATION, BASAL GANGLIA DISEASE, AND SEIZURES	Pettigrew syndrome	BEFREE	23756445, 29740252, 30714330		★☆☆☆☆ Found in Text Mining only
DANDY-WALKER MALFORMATION WITH MENTAL RETARDATION, BASAL GANGLIA DISEASE, AND SEIZURES	Pettigrew syndrome	ORPHANET_DG	23756445		★☆☆☆☆ Found in Text Mining only
DANDY-WALKER MALFORMATION WITH MENTAL RETARDATION, BASAL GANGLIA DISEASE, AND SEIZURES	Pettigrew syndrome	CLINVAR_DG			★☆☆☆☆ Found in Text Mining only
Dandy-Walker Syndrome	Dandy-Walker Syndrome	BEFREE	23756445		★☆☆☆☆ Found in Text Mining only
Degenerative polyarthritis	Arthritis	BEFREE	31523167		★☆☆☆☆ Found in Text Mining only
Dwarfism	Dwarfism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Endometriosis	Endometriosis	Pubtator	40165344	Associate	★☆☆☆☆ Found in Text Mining only
Fried syndrome	Fried Syndrome	Orphanet			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Global developmental delay	Developmental Delay	BEFREE	22210230		★☆☆☆☆ Found in Text Mining only
Global developmental delay	Developmental Delay	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hearing Loss, High-Frequency	Hearing Loss	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hydrocephalus	Hydrocephalus	BEFREE	17617514		★☆☆☆☆ Found in Text Mining only
Hydrocephalus	Hydrocephalus	Pubtator	17617514, 34092257	Associate	★☆☆☆☆ Found in Text Mining only
Hydrocephalus	Hydrocephalus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Intellectual Disability	Mental retardation	BEFREE	10398241, 17617514, 23756445, 30714330		★☆☆☆☆ Found in Text Mining only
Intellectual Disability	Intellectual developmental disorder	Pubtator	17186471, 17617514, 23756445, 25649377	Associate	★☆☆☆☆ Found in Text Mining only
Leiomyoma	Leiomyoma	Pubtator	21685710	Associate	★☆☆☆☆ Found in Text Mining only
Little`s Disease	Spastic diplegia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Lung diseases	Lung Diseases	BEFREE	26635082		★☆☆☆☆ Found in Text Mining only
Lung Diseases	Lung disease	Pubtator	26635082	Associate	★☆☆☆☆ Found in Text Mining only
Macrocephaly	Macrocephaly	HPO_DG			★☆☆☆☆ Found in Text Mining only
Macrostomia	Macrostomia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Macrotia	Macrotia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of breast	Breast Cancer	BEFREE	31019021		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of prostate	Prostate cancer	BEFREE	25530379, 25982801		★☆☆☆☆ Found in Text Mining only
Mammary Neoplasms	Mammary Neoplasms	BEFREE	11034073		★☆☆☆☆ Found in Text Mining only
Melanoma	Melanoma	Pubtator	31712557	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Mental Retardation	Mental retardation	BEFREE	17617514, 30714330		★☆☆☆☆ Found in Text Mining only
Mental Retardation, X-Linked	Mental retardation	BEFREE	17186471, 17617514, 18428203, 22210230, 30714330		★☆☆☆☆ Found in Text Mining only
Mental Retardation, X-Linked Nonsyndromic	Mental retardation	CLINGEN_DG	10398241, 12599187, 17186471, 17617514, 18428203, 2018058, 20203623, 22210230, 23756445, 25128028, 25649377, 27411398		★☆☆☆☆ Found in Text Mining only
Microcephaly	Microcephaly	HPO_DG			★☆☆☆☆ Found in Text Mining only
Miscarriage	Miscarriage	BEFREE	27272212, 29864578		★☆☆☆☆ Found in Text Mining only
Moderate intellectual disability	Mental retardation	HPO_DG			★☆☆☆☆ Found in Text Mining only
Myopathy	Myopathy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	11034073		★☆☆☆☆ Found in Text Mining only
Neurodevelopmental Disorders	Neurodevelopmental Disorders	BEFREE	30714330		★☆☆☆☆ Found in Text Mining only
Osteoarthritis	Osteoarthritis	Pubtator	31523167	Associate	★☆☆☆☆ Found in Text Mining only
Prostate carcinoma	Prostate cancer	BEFREE	25530379, 25982801		★☆☆☆☆ Found in Text Mining only
Prostatic Neoplasms	Prostatic neoplasm	Pubtator	33672425	Associate	★☆☆☆☆ Found in Text Mining only
Psychomotor Disorders	Psychiatric disorders	Pubtator	22210230	Associate	★☆☆☆☆ Found in Text Mining only
Scoliosis, unspecified	Scoliosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Seizures	Seizures	Pubtator	23756445	Associate	★☆☆☆☆ Found in Text Mining only
Sensorineural Hearing Loss (disorder)	Hearing Loss	HPO_DG			★☆☆☆☆ Found in Text Mining only
Severe intellectual disability	Mental retardation	HPO_DG			★☆☆☆☆ Found in Text Mining only
Stomach Neoplasms	Stomach neoplasms	Pubtator	33067881	Associate	★☆☆☆☆ Found in Text Mining only
Strabismus	Strabismus	HPO_DG			★☆☆☆☆ Found in Text Mining only
X-linked intellectual disability-Dandy-Walker malformation-basal ganglia disease-seizures syndrome	Intellectual Disability-Dandy-Walker Malformation-Basal Ganglia Disease-Seizures Syndrome, X-Linked	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
X-linked intellectual disability-hypotonia-facial dysmorphism-aggressive behavior syndrome	Intellectual Disability-Hypotonia-Facial Dysmorphism-Aggressive Behavior Syndrome, X-Linked	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations